chr7-103393310-G-A

Variant names:

• chr7-103393310-G-A
• rs7804867
• NM_198999.3:c.972-244C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198999.3(SLC26A5):​c.972-244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,076 control chromosomes in the GnomAD database, including 2,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2528 hom., cov: 31)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.15
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-103393310-G-A is Benign according to our data. Variant chr7-103393310-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.972-244C>T		intron_variant	Intron 9 of 19	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.972-244C>T		intron_variant	Intron 9 of 19	1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.972-244C>T		intron_variant	Intron 7 of 17	1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.972-244C>T		intron_variant	Intron 7 of 16	1		ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26499 AN: 151960 Hom.: 2521 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.174 AC: 26522 AN: 152076 Hom.: 2528 Cov.: 31 AF XY: 0.181 AC XY: 13440 AN XY: 74342

African (AFR) AF: 0.122 AC: 5057 AN: 41518

American (AMR) AF: 0.196 AC: 2993 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.296 AC: 1532 AN: 5176

South Asian (SAS) AF: 0.214 AC: 1027 AN: 4810

European-Finnish (FIN) AF: 0.273 AC: 2880 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12102 AN: 67954

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.174 Hom.: 9562

Bravo AF: 0.167

Asia WGS AF: 0.224 AC: 776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0080
DANN	Benign	0.69
PhyloP100		-4.1
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: rs7804867; hg19: chr7-103033757;