rs727503431

chr7-107710179-C-Gchr7-107710179-C-T

Variant summary

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

The NM_000441.2(SLC26A4):c.2215C>G(p.Gln739Glu) 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. 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. Synonymous variant affecting the same amino acid position (i.e. Q739Q) 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: 2.40

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=0.19435802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A4	NM_000441.2	c.2215C>G	p.Gln739Glu	missense_variant	19/21	ENST00000644269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A4	ENST00000644269.2	c.2215C>G	p.Gln739Glu	missense_variant	19/21		NM_000441.2	P1
SLC26A4	ENST00000492030.2	n.401C>G		non_coding_transcript_exon_variant	4/6	5
SLC26A4	ENST00000644846.1	c.*117C>G		3_prime_UTR_variant, NMD_transcript_variant	8/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Benign	0.082	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	0.92	D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.040	N;.
REVEL	Benign	0.23
Sift	Benign	0.29	T;.
Sift4G	Benign	0.76	T;.
Polyphen		0.0	B;B
Vest4		0.35
MutPred		0.34		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.92
MPC		0.011
ClinPred		0.28	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.53

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: rs727503431; hg19: chr7-107350624;