chr7-107683500-A-C

Position:

• chr7-107683500-A-C

Variant summary

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

The NM_000441.2(SLC26A4):​c.964A>C​(p.Asn322His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N322D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26020592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A4	NM_000441.2	c.964A>C	p.Asn322His	missense_variant	8/21	ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.964A>C	p.Asn322His	missense_variant	8/21		NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Uncertain	0.50	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.0063
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.28
Sift	Benign	0.039	D;.
Sift4G	Benign	0.088	T;.
Polyphen		0.0010	B;B
Vest4		0.28
MutPred		0.42		Loss of ubiquitination at K321 (P = 0.063);Loss of ubiquitination at K321 (P = 0.063);
MVP		0.93
MPC		0.011
ClinPred		0.54	D
GERP RS		3.1
Varity_R		0.30
gMVP		0.72

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: chr7-107323945;