chr1-43736300-C-G

Variant names:

• chr1-43736300-C-G
• NM_006279.5:c.38C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_006279.5(ST3GAL3):​c.38C>G​(p.Ala13Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A13D) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ST3GAL3 NM_006279.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29

Genes affected

ST3GAL3 (HGNC:10866): (ST3 beta-galactoside alpha-2,3-sialyltransferase 3) The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ENSG00000284989 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-43736300-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 30587.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.35254812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST3GAL3	NM_006279.5	c.38C>G	p.Ala13Gly	missense_variant	Exon 2 of 12	ENST00000347631.8	NP_006270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST3GAL3	ENST00000347631.8	c.38C>G	p.Ala13Gly	missense_variant	Exon 2 of 12	5	NM_006279.5	ENSP00000317192.6
ENSG00000284989	ENST00000645057.1	n.*1360C>G		non_coding_transcript_exon_variant	Exon 16 of 26			ENSP00000494063.1
ENSG00000284989	ENST00000645057.1	n.*1360C>G		3_prime_UTR_variant	Exon 16 of 26			ENSP00000494063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;.;.
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.35	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.8	L;L;L;L;L;L;L;.;.;.;L;.;L;L;L;L;.;L;.;.;.;L;.;.;L;L;L;L;L;L;L;L;L;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.92	N;N;N;D;D;N;N;.;.;.;N;.;N;.;N;.;.;N;.;N;.;.;N;.;D;D;N;N;N;N;D;N;D;N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D;T;D;D;T;D;.;.;.;D;.;D;.;D;.;.;D;.;D;.;.;D;.;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.060	T;T;T;D;D;D;D;.;.;.;T;.;D;.;T;.;.;D;.;D;.;.;T;.;D;D;T;D;D;D;D;T;D;D
Polyphen		0.39	B;P;P;.;P;P;B;.;.;.;.;.;P;P;P;B;.;P;.;.;.;B;.;.;P;P;P;P;.;P;P;B;.;P
Vest4		0.55
MutPred		0.50		Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);Loss of stability (P = 0.0316);
MVP		0.62
MPC		0.58
ClinPred		0.87	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.82

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: chr1-44201971;