7-107661709-C-T

Variant names:

• chr7-107661709-C-T
• rs397516430
• NM_000441.2:c.68C>T

Variant summary

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

The NM_000441.2(SLC26A4):​c.68C>T​(p.Ser23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

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]

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

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=0.39405426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.68C>T	p.Ser23Leu	missense_variant	Exon 2 of 21	ENST00000644269.2	NP_000432.1
SLC26A4-AS1	NR_028137.1	n.90G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.68C>T	p.Ser23Leu	missense_variant	Exon 2 of 21		NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1415600 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700714

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: 0.00

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	0.11
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.8	D;.;D
REVEL	Uncertain	0.34
Sift	Benign	0.13	T;.;T
Sift4G	Benign	0.19	T;.;T
Polyphen		0.32	B;B;.
Vest4		0.35
MutPred		0.38		Loss of phosphorylation at S23 (P = 0.0298);Loss of phosphorylation at S23 (P = 0.0298);Loss of phosphorylation at S23 (P = 0.0298);
MVP		0.90
MPC		0.014
ClinPred		0.85	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.55

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: rs397516430; hg19: chr7-107302154; COSMIC: COSV99707706;