6-31878964-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_025257.3(SLC44A4):​c.17G>A​(p.Arg6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SLC44A4
NM_025257.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.853
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04110807).
BS2
High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC44A4NM_025257.3 linkc.17G>A p.Arg6Gln missense_variant Exon 1 of 21 ENST00000229729.11 NP_079533.2 Q53GD3-1A0A140VJH4
SLC44A4NM_001178044.2 linkc.17G>A p.Arg6Gln missense_variant Exon 1 of 20 NP_001171515.1 Q53GD3-4
EHMT2-AS1NR_174947.1 linkn.271+886C>T intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC44A4ENST00000229729.11 linkc.17G>A p.Arg6Gln missense_variant Exon 1 of 21 1 NM_025257.3 ENSP00000229729.6 Q53GD3-1
SLC44A4ENST00000414427.1 linkc.2G>A p.Arg1Gln missense_variant Exon 1 of 13 5 ENSP00000398901.1 H0Y5I3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152092
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250636
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135532
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461524
Hom.:
0
Cov.:
33
AF XY:
0.00000825
AC XY:
6
AN XY:
727076
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152092
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000385
Hom.:
707
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.20
DANN
Benign
0.86
DEOGEN2
Benign
0.0051
T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0029
N
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.041
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.090
N;N
REVEL
Benign
0.015
Sift
Benign
0.29
T;T
Sift4G
Benign
0.72
T;T
Polyphen
0.0070
B;.
Vest4
0.055
MutPred
0.18
Gain of glycosylation at K4 (P = 0.1238);Gain of glycosylation at K4 (P = 0.1238);
MVP
0.030
MPC
0.25
ClinPred
0.054
T
GERP RS
-3.2
Varity_R
0.029
gMVP
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2075798; hg19: chr6-31846741; API