7-103374457-G-C

Variant names:

• chr7-103374457-G-C
• NM_198999.3:c.2177C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198999.3(SLC26A5):​c.2177C>G​(p.Ala726Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC26A5 NM_198999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10075739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.2177C>G	p.Ala726Gly	missense_variant	Exon 20 of 20	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.2177C>G	p.Ala726Gly	missense_variant	Exon 20 of 20	1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.2183C>G	p.Ala728Gly	missense_variant	Exon 18 of 18	1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.2087C>G	p.Ala696Gly	missense_variant	Exon 17 of 17	1		ENSP00000377324.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.0
DANN	Benign	0.94
DEOGEN2	Benign	0.15	.;T;.;T;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.86	.;D;D;D;D;.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.10	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.71	N;N;N;.;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D;D;.;D;D;D
Sift4G	Uncertain	0.049	D;D;D;D;D;D;D
Polyphen		0.011	.;B;.;.;.;.;.
Vest4		0.16
MutPred		0.18		.;Loss of glycosylation at S729 (P = 0.1501);.;.;.;.;.;
MVP		0.68
MPC		0.13
ClinPred		0.054	T
GERP RS		1.9
Varity_R		0.065
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-103014904;