chr5-140367427-T-C

Position:

• chr5-140367427-T-C

Variant summary

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

The NM_031467.3(SLC4A9):​c.2021T>C​(p.Leu674Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A9 NM_031467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07

Genes affected

SLC4A9 (HGNC:11035): (solute carrier family 4 member 9) The protein encoded by this gene is a membrane protein involved in anion exchange. Expression of this gene is mostly limited to the kidney. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A9	NM_031467.3	c.2021T>C	p.Leu674Pro	missense_variant	15/22	ENST00000506757.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A9	ENST00000506757.7	c.2021T>C	p.Leu674Pro	missense_variant	15/22	1	NM_031467.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.2021T>C (p.L674P) alteration is located in exon 15 (coding exon 15) of the SLC4A9 gene. This alteration results from a T to C substitution at nucleotide position 2021, causing the leucine (L) at amino acid position 674 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;.;.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.6	.;.;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.0	N;D;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.99	D;.;D;D
Vest4		0.44
MutPred		0.49		.;.;.;Gain of disorder (P = 0.0042);
MVP		0.86
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.26
gMVP		0.70

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: chr5-139747012;