rs2242665

Variant names:

• chr6-31871532-C-A
• NM_025257.3:c.559G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31871532-C-A
• chr6-31871532-C-G
• chr6-31871532-C-T

Variant summary

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

The NM_025257.3(SLC44A4):​c.559G>T​(p.Val187Phe) 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. 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. V187I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC44A4 NM_025257.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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]

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=0.06566283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.559G>T	p.Val187Phe	missense_variant	Exon 8 of 21	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.433G>T	p.Val145Phe	missense_variant	Exon 7 of 20		NP_001171515.1
SLC44A4	NM_001178045.2	c.331G>T	p.Val111Phe	missense_variant	Exon 8 of 21		NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.559G>T	p.Val187Phe	missense_variant	Exon 8 of 21	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.544G>T	p.Val182Phe	missense_variant	Exon 8 of 13	5		ENSP00000398901.1
SLC44A4	ENST00000375562.8	c.433G>T	p.Val145Phe	missense_variant	Exon 7 of 20	2		ENSP00000364712.4
SLC44A4	ENST00000544672.5	c.331G>T	p.Val111Phe	missense_variant	Exon 8 of 21	2		ENSP00000444109.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0048	T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.29	N;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.87	N;N;N;.
REVEL	Benign	0.013
Sift	Benign	0.13	T;T;T;.
Sift4G	Benign	0.45	T;T;T;.
Polyphen		0.0	B;.;.;.
Vest4		0.23
MutPred		0.36		Loss of loop (P = 0.1242);.;.;.;
MVP		0.030
MPC		0.30
ClinPred		0.064	T
GERP RS		0.52
Varity_R		0.036
gMVP		0.63

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: chr6-31839309;