rs786205569

Variant names:

• chr4-71440650-A-C
• NM_001098484.3:c.842A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-71440650-A-C
• chr4-71440650-A-T

Variant summary

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

The NM_001098484.3(SLC4A4):​c.842A>C​(p.Asp281Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,848 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC4A4 NM_001098484.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

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, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.842A>C	p.Asp281Ala	missense_variant	Exon 8 of 26	ENST00000264485.11	NP_001091954.1
SLC4A4	NM_003759.4	c.710A>C	p.Asp237Ala	missense_variant	Exon 5 of 23	ENST00000340595.4	NP_003750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.842A>C	p.Asp281Ala	missense_variant	Exon 8 of 26	1	NM_001098484.3	ENSP00000264485.5
SLC4A4	ENST00000340595.4	c.710A>C	p.Asp237Ala	missense_variant	Exon 5 of 23	1	NM_003759.4	ENSP00000344272.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727228

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;D;.;.;.;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Pathogenic	3.1	M;M;M;M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.0	.;D;D;D;D;D
REVEL	Pathogenic	0.93
Sift	Uncertain	0.0020	.;D;D;D;D;D
Sift4G	Uncertain	0.0060	.;D;D;D;D;D
Polyphen		0.92	P;P;.;D;D;P
Vest4		0.71, 0.75, 0.75, 0.76, 0.74
MutPred		0.51		Gain of MoRF binding (P = 0.0356);Gain of MoRF binding (P = 0.0356);Gain of MoRF binding (P = 0.0356);Gain of MoRF binding (P = 0.0356);.;.;
MVP		0.86
MPC		1.4
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.84
gMVP		0.86

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: chr4-72306367;