7-103374371-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_198999.3(SLC26A5):c.*28A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,611,808 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (5 hom.)
• Consequence: SLC26A5 NM_198999.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.419

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-103374371-T-C is Benign according to our data. Variant chr7-103374371-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1195713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00136 (207/152308) while in subpopulation NFE AF= 0.00248 (169/68032). AF 95% confidence interval is 0.00218. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A5	NM_198999.3	c.*28A>G		3_prime_UTR_variant	20/20	ENST00000306312.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A5	ENST00000306312.8	c.*28A>G		3_prime_UTR_variant	20/20	1	NM_198999.3	P4

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00112 AC: 280 AN: 250750 Hom.: 0 AF XY: 0.00111 AC XY: 151 AN XY: 135532

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00221

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.00211 AC: 3081 AN: 1459500 Hom.: 5 Cov.: 32 AF XY: 0.00204 AC XY: 1479 AN XY: 726040

Gnomad4 AFR exome AF: 0.000449

Gnomad4 AMR exome AF: 0.000381

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.000994 AC XY: 74 AN XY: 74468

Gnomad4 AFR AF: 0.000626

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00140 Hom.: 0

Bravo AF: 0.00146

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 15, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.39
Dann	Benign	0.73

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: rs375753696; hg19: chr7-103014818;