7-103379166-A-G

Variant names:

• chr7-103379166-A-G
• rs12705120
• NM_198999.3:c.1677+77T>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.1677+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 957,238 control chromosomes in the GnomAD database, including 474,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73665 hom., cov: 30)
  • Exomes 𝑓: 1.0 (400745 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.765
• Publications: 5 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=-0.83).
• BP6: Variant 7-103379166-A-G is Benign according to our data. Variant chr7-103379166-A-G is described in ClinVar as Benign. ClinVar VariationId is 1174332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1677+77T>C		intron	N/A	NP_945350.1
	SLC26A5	NM_001167962.2		c.1581+77T>C		intron	N/A	NP_001161434.1
	SLC26A5	NM_206883.3		c.1677+77T>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.1677+77T>C		intron	N/A	ENSP00000304783.3
	SLC26A5	ENST00000393727.5	TSL:1	c.1677+77T>C		intron	N/A	ENSP00000377328.1
	SLC26A5	ENST00000393723.2	TSL:1	c.1581+77T>C		intron	N/A	ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149588 AN: 152110 Hom.: 73610 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.994

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.982

GnomAD4 exome AF: 0.998 AC: 803210 AN: 805010 Hom.: 400745 AF XY: 0.998 AC XY: 425883 AN XY: 426660

African (AFR) AF: 0.941 AC: 19545 AN: 20780

American (AMR) AF: 0.996 AC: 43258 AN: 43444

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 21912 AN: 21912

East Asian (EAS) AF: 1.00 AC: 36577 AN: 36578

South Asian (SAS) AF: 1.00 AC: 72552 AN: 72560

European-Finnish (FIN) AF: 1.00 AC: 52020 AN: 52020

Middle Eastern (MID) AF: 0.996 AC: 4466 AN: 4484

European-Non Finnish (NFE) AF: 1.00 AC: 514419 AN: 514562

Other (OTH) AF: 0.995 AC: 38461 AN: 38670

GnomAD4 genome AF: 0.983 AC: 149701 AN: 152228 Hom.: 73665 Cov.: 30 AF XY: 0.984 AC XY: 73254 AN XY: 74438

African (AFR) AF: 0.943 AC: 39130 AN: 41500

American (AMR) AF: 0.994 AC: 15201 AN: 15288

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 1.00 AC: 4827 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67995 AN: 68026

Other (OTH) AF: 0.982 AC: 2077 AN: 2114

Alfa AF: 0.991 Hom.: 8730

Bravo AF: 0.981

Asia WGS AF: 0.997 AC: 3465 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 22, 2018

GeneDx

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	-0.83
CADD	Benign	1.9
DANN	Benign	0.33
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12705120; hg19: chr7-103019613;