chr7-103412988-A-G

Variant names:

• chr7-103412988-A-G
• rs7779997
• NM_198999.3:c.403+14T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198999.3(SLC26A5):​c.403+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,507,310 control chromosomes in the GnomAD database, including 65,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (14709 hom., cov: 31)
  • Exomes 𝑓: 0.26 (50312 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0920
• Publications: 10 publications found

Genes affected

SLC26A5 (HGNC:9359): (solute carrier family 26 member 5) This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

SLC26A5 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 61

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-103412988-A-G is Benign according to our data. Variant chr7-103412988-A-G is described in ClinVar as Benign. ClinVar VariationId is 48339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	NM_198999.3	MANE Select	c.403+14T>C		intron	N/A	NP_945350.1
	SLC26A5	NM_001167962.2		c.403+14T>C		intron	N/A	NP_001161434.1
	SLC26A5	NM_206883.3		c.403+14T>C		intron	N/A	NP_996766.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	ENST00000306312.8	TSL:1 MANE Select	c.403+14T>C		intron	N/A	ENSP00000304783.3
	SLC26A5	ENST00000393727.5	TSL:1	c.403+14T>C		intron	N/A	ENSP00000377328.1
	SLC26A5	ENST00000393723.2	TSL:1	c.403+14T>C		intron	N/A	ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58081 AN: 151920 Hom.: 14664 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.305 AC: 76450 AN: 250458 AF XY: 0.296

Gnomad AFR exome AF: 0.739

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.410

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.256 AC: 347005 AN: 1355272 Hom.: 50312 Cov.: 21 AF XY: 0.257 AC XY: 174891 AN XY: 680444

African (AFR) AF: 0.743 AC: 23225 AN: 31266

American (AMR) AF: 0.310 AC: 13821 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4343 AN: 25536

East Asian (EAS) AF: 0.392 AC: 15327 AN: 39122

South Asian (SAS) AF: 0.347 AC: 29142 AN: 84010

European-Finnish (FIN) AF: 0.302 AC: 16097 AN: 53286

Middle Eastern (MID) AF: 0.197 AC: 1096 AN: 5566

European-Non Finnish (NFE) AF: 0.225 AC: 228451 AN: 1015098

Other (OTH) AF: 0.273 AC: 15503 AN: 56866

GnomAD4 genome AF: 0.383 AC: 58187 AN: 152038 Hom.: 14709 Cov.: 31 AF XY: 0.384 AC XY: 28524 AN XY: 74320

African (AFR) AF: 0.722 AC: 29919 AN: 41446

American (AMR) AF: 0.279 AC: 4265 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3464

East Asian (EAS) AF: 0.403 AC: 2087 AN: 5174

South Asian (SAS) AF: 0.349 AC: 1680 AN: 4820

European-Finnish (FIN) AF: 0.315 AC: 3331 AN: 10562

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15434 AN: 67988

Other (OTH) AF: 0.305 AC: 644 AN: 2114

Alfa AF: 0.298 Hom.: 2461

Bravo AF: 0.394

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

403+14T>C in Intron 05 of SLC26A5: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 29.3% (1096/3738) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs7779997).

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal recessive nonsyndromic hearing loss 61 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7779997; hg19: chr7-103053435;