chr6-31878964-C-G

Variant names:

• chr6-31878964-C-G
• rs2075798
• NM_025257.3:c.17G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025257.3(SLC44A4):​c.17G>C​(p.Arg6Pro) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC44A4 NM_025257.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05108726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.17G>C	p.Arg6Pro	missense_variant	Exon 1 of 21	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.17G>C	p.Arg6Pro	missense_variant	Exon 1 of 20		NP_001171515.1
EHMT2-AS1	NR_174947.1	n.271+886C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.17G>C	p.Arg6Pro	missense_variant	Exon 1 of 21	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.2G>C	p.Arg1Pro	missense_variant	Exon 1 of 13	5		ENSP00000398901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.20
DANN	Benign	0.74
DEOGEN2	Benign	0.0084	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.17	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.015
Sift	Benign	0.089	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0020	B;.
Vest4		0.044
MutPred		0.18		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.061
MPC		0.32
ClinPred		0.077	T
GERP RS		-3.2
Varity_R		0.14
gMVP		0.60

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: rs2075798; hg19: chr6-31846741;