7-107674320-C-G

Position:

• chr7-107674320-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM5

The NM_000441.2(SLC26A4):​c.572C>G​(p.Ala191Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A191V) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A4 NM_000441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 3 uncertain in NM_000441.2
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr7-107674320-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43561.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Likely_pathogenic=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.572C>G	p.Ala191Gly	missense_variant	5/21	ENST00000644269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.572C>G	p.Ala191Gly	missense_variant	5/21		NM_000441.2	P1

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	0.12
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;D
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.012
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	.;T
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	1.9	L;L
MutationTaster	Benign	0.55	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.9	N;.
REVEL	Uncertain	0.48
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.011	D;.
Polyphen		0.032	B;B
Vest4		0.42
MutPred		0.54		Loss of stability (P = 0.0837);Loss of stability (P = 0.0837);
MVP		0.96
MPC		0.011
ClinPred		0.64	D
GERP RS		5.1
Varity_R		0.39
gMVP		0.71

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: chr7-107314765;