1-31424830-T-A

Position:

• chr1-31424830-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178865.5(SERINC2):​c.349T>A​(p.Cys117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SERINC2 NM_178865.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.742

Genes affected

SERINC2 (HGNC:23231): (serine incorporator 2) Predicted to be involved in several processes, including phosphatidylserine metabolic process; positive regulation of CDP-diacylglycerol-serine O-phosphatidyltransferase activity; and positive regulation of serine C-palmitoyltransferase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC2	NM_178865.5	c.349T>A	p.Cys117Ser	missense_variant	3/10	ENST00000373709.8	NP_849196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERINC2	ENST00000373709.8	c.349T>A	p.Cys117Ser	missense_variant	3/10	1	NM_178865.5	ENSP00000362813	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2021

The c.376T>A (p.C126S) alteration is located in exon 4 (coding exon 4) of the SERINC2 gene. This alteration results from a T to A substitution at nucleotide position 376, causing the cysteine (C) at amino acid position 126 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0079	.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;.;M;.
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.55	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.034	.;.;B;.
Vest4		0.52
MutPred		0.55		.;.;Gain of disorder (P = 3e-04);.;
MVP		0.15
MPC		0.45
ClinPred		0.84	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr1-31897677;