rs955050835

Variant names:

• chr3-27391797-C-G
• NM_001321103.2:c.3129G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-27391797-C-G
• chr3-27391797-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001321103.2(SLC4A7):​c.3129G>C​(p.Met1043Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,046 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC4A7 NM_001321103.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

Genes affected

SLC4A7 (HGNC:11033): (solute carrier family 4 member 7) This locus encodes a sodium bicarbonate cotransporter. The encoded transmembrane protein appears to transport sodium and bicarbonate ions in a 1:1 ratio, and is thus considered an electroneutral cotransporter. The encoded protein likely plays a critical role in regulation of intracellular pH involved in visual and auditory sensory transmission. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A7	NM_001321103.2	c.3129G>C	p.Met1043Ile	missense_variant	Exon 21 of 26	ENST00000454389.6	NP_001308032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A7	ENST00000454389.6	c.3129G>C	p.Met1043Ile	missense_variant	Exon 21 of 26	1	NM_001321103.2	ENSP00000390394.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438046 Hom.: 0 Cov.: 26 AF XY: 0.00000279 AC XY: 2 AN XY: 715702

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: 0.00000183

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;.;D;.;.;.;.;.;.;.;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Uncertain	2.6	.;.;M;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	.;D;D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0010	.;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.95, 1.0	.;.;P;D;.;.;.;.;.;P;.
Vest4		0.69
MutPred		0.80		.;.;Loss of ubiquitination at K1030 (P = 0.093);.;.;.;.;.;.;.;.;
MVP		0.48
MPC		0.85
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.69
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-27433288;