chr7-103423590-C-G

Variant names:

• chr7-103423590-C-G
• rs6972505
• NM_198999.3:c.-53-2023G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198999.3(SLC26A5):​c.-53-2023G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,908 control chromosomes in the GnomAD database, including 22,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22581 hom., cov: 31)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.-53-2023G>C		intron_variant	Intron 2 of 19	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.-53-2023G>C		intron_variant	Intron 2 of 19	1	NM_198999.3	ENSP00000304783.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77755 AN: 151790 Hom.: 22528 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.513 AC: 77877 AN: 151908 Hom.: 22581 Cov.: 31 AF XY: 0.516 AC XY: 38332 AN XY: 74216

African (AFR) AF: 0.780 AC: 32353 AN: 41458

American (AMR) AF: 0.513 AC: 7830 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3464

East Asian (EAS) AF: 0.710 AC: 3648 AN: 5140

South Asian (SAS) AF: 0.601 AC: 2893 AN: 4812

European-Finnish (FIN) AF: 0.373 AC: 3932 AN: 10528

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24614 AN: 67934

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.432 Hom.: 1904

Bravo AF: 0.529

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.31
PhyloP100		-0.056
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: rs6972505; hg19: chr7-103064037;