rs10273883

Positions:

• chr7-103377569-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198999.3(SLC26A5):​c.1986+30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,602,314 control chromosomes in the GnomAD database, including 782,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (67096 hom., cov: 31)
  • Exomes 𝑓: 0.99 (715730 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-103377569-A-G is Benign according to our data. Variant chr7-103377569-A-G is described in ClinVar as [Benign]. Clinvar id is 1235817.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A5	NM_198999.3	c.1986+30T>C		intron_variant		ENST00000306312.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A5	ENST00000306312.8	c.1986+30T>C		intron_variant		1	NM_198999.3	P4

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142032 AN: 152110 Hom.: 67062 Cov.: 31

Gnomad AFR AF: 0.771

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.952

GnomAD3 exomes AF: 0.982 AC: 246603 AN: 251042 Hom.: 121518 AF XY: 0.987 AC XY: 133971 AN XY: 135712

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.991

GnomAD4 exome AF: 0.993 AC: 1439770 AN: 1450086 Hom.: 715730 Cov.: 28 AF XY: 0.994 AC XY: 717823 AN XY: 722228

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.983

GnomAD4 genome AF: 0.934 AC: 142126 AN: 152228 Hom.: 67096 Cov.: 31 AF XY: 0.936 AC XY: 69680 AN XY: 74420

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.953

Alfa AF: 0.984 Hom.: 82206

Bravo AF: 0.923

Asia WGS AF: 0.985 AC: 3424 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 61 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs10273883; hg19: chr7-103018016;