rs66928926

Positions:

• chr7-103376685-CAGA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_198999.3(SLC26A5):​c.2041+120_2041+122delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 779,124 control chromosomes in the GnomAD database, including 2,881 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1609 hom., cov: 30)
  • Exomes 𝑓: 0.047 (1272 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.539

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-103376685-CAGA-C is Benign according to our data. Variant chr7-103376685-CAGA-C is described in ClinVar as [Benign]. Clinvar id is 1287837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.2041+120_2041+122delTCT		intron_variant		ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.2041+120_2041+122delTCT		intron_variant		1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.2047+120_2047+122delTCT		intron_variant		1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.1951+120_1951+122delTCT		intron_variant		1		ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16188 AN: 151858 Hom.: 1610 Cov.: 30

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0852

GnomAD4 exome AF: 0.0470 AC: 29454 AN: 627148 Hom.: 1272 AF XY: 0.0440 AC XY: 14661 AN XY: 332872

Gnomad4 AFR exome AF: 0.285

Gnomad4 AMR exome AF: 0.0396

Gnomad4 ASJ exome AF: 0.0175

Gnomad4 EAS exome AF: 0.0000661

Gnomad4 SAS exome AF: 0.00851

Gnomad4 FIN exome AF: 0.0931

Gnomad4 NFE exome AF: 0.0432

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.107 AC: 16208 AN: 151976 Hom.: 1609 Cov.: 30 AF XY: 0.105 AC XY: 7823 AN XY: 74286

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0823 Hom.: 125

Bravo AF: 0.112

Asia WGS AF: 0.0180 AC: 62 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs66928926; hg19: chr7-103017132;