NM_025257.3:c.34G>A

Variant names:

• chr6-31878947-C-T
• NM_025257.3:c.34G>A

Variant summary

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

The NM_025257.3(SLC44A4):​c.34G>A​(p.Ala12Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC44A4 NM_025257.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

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=0.088722825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.34G>A	p.Ala12Thr	missense_variant	Exon 1 of 21	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.34G>A	p.Ala12Thr	missense_variant	Exon 1 of 20		NP_001171515.1
EHMT2-AS1	NR_174947.1	n.271+869C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.34G>A	p.Ala12Thr	missense_variant	Exon 1 of 21	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.19G>A	p.Ala7Thr	missense_variant	Exon 1 of 13	5		ENSP00000398901.1

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 provided Uncertain:1

Apr 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 12 of the SLC44A4 protein (p.Ala12Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC44A4-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.8
DANN	Benign	0.80
DEOGEN2	Benign	0.0052	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.067	N
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.049
Sift	Benign	0.51	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.28	B;.
Vest4		0.28
MutPred		0.12		Gain of phosphorylation at A12 (P = 0.0191);Gain of phosphorylation at A12 (P = 0.0191);
MVP		0.088
MPC		0.22
ClinPred		0.16	T
GERP RS		2.7
Varity_R		0.045
gMVP		0.62

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: chr6-31846724;