rs35548413

Variant names:

• chr7-107704355-G-C
• NM_000441.2:c.2059G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-107704355-G-C
• chr7-107704355-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000441.2(SLC26A4):​c.2059G>C​(p.Asp687His) variant causes a missense change. The variant allele was found at a frequency of 0.000000802 in 1,247,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 8.0e-7 (0 hom.)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39

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 5 ACMG points.

• PM1: In a domain STAS (size 194) in uniprot entity S26A4_HUMAN there are 17 pathogenic changes around while only 4 benign (81%) in NM_000441.2
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.2059G>C	p.Asp687His	missense_variant	Exon 18 of 21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.2059G>C	p.Asp687His	missense_variant	Exon 18 of 21		NM_000441.2	ENSP00000494017.1
SLC26A4	ENST00000492030.2	n.346G>C		non_coding_transcript_exon_variant	Exon 3 of 6	5
SLC26A4	ENST00000644846.1	n.744+2298G>C		intron_variant	Intron 7 of 9			ENSP00000494344.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.02e-7 AC: 1 AN: 1247172 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 629090

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: 0.00000109

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	0.20
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Pathogenic	0.77
Sift	Uncertain	0.024	D;.
Sift4G	Uncertain	0.011	D;.
Polyphen		0.91	P;P
Vest4		0.71
MutPred		0.41		Gain of MoRF binding (P = 0.0594);Gain of MoRF binding (P = 0.0594);
MVP		0.98
MPC		0.067
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.49
gMVP		0.78

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: chr7-107344800;