NM_025257.3:c.31G>T

Variant names:

• chr6-31878950-C-A
• rs11551744
• NM_025257.3:c.31G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025257.3(SLC44A4):​c.31G>T​(p.Glu11*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: SLC44A4 NM_025257.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025257.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	NM_025257.3	MANE Select	c.31G>T	p.Glu11*	stop_gained	Exon 1 of 21	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.31G>T	p.Glu11*	stop_gained	Exon 1 of 20	NP_001171515.1	Q53GD3-4
	EHMT2-AS1	NR_174947.1		n.271+872C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.31G>T	p.Glu11*	stop_gained	Exon 1 of 21	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000414427.1	TSL:5	c.16G>T	p.Glu6*	stop_gained	Exon 1 of 13	ENSP00000398901.1	H0Y5I3
	SLC44A4	ENST00000882851.1		c.31G>T	p.Glu11*	stop_gained	Exon 1 of 21	ENSP00000552910.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.11
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.076	N
PhyloP100		0.28
Vest4		0.14
GERP RS		1.5
PromoterAI		0.011	Neutral
Mutation Taster		=54/146	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs11551744; hg19: chr6-31846727;