chr7-107694676-G-A

Position:

• chr7-107694676-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000441.2(SLC26A4):​c.1397G>A​(p.Cys466Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3512122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.1397G>A	p.Cys466Tyr	missense_variant	12/21	ENST00000644269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.1397G>A	p.Cys466Tyr	missense_variant	12/21		NM_000441.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461288 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726972

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pendred syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Sep 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.36	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.81	.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	-0.63	N;N
MutationTaster	Benign	0.63	D;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.46
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.14	B;B
Vest4		0.76
MutPred		0.36		Gain of solvent accessibility (P = 0.1116);Gain of solvent accessibility (P = 0.1116);
MVP		0.80
MPC		0.018
ClinPred		0.43	T
GERP RS		5.7
Varity_R		0.31
gMVP		0.59

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: rs1554359686; hg19: chr7-107335121;