chr20-44500404-G-C

Position:

• chr20-44500404-G-C

Variant summary

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

The NM_006811.4(SERINC3):​c.1314C>G​(p.Ser438Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERINC3 NM_006811.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

Genes affected

SERINC3 (HGNC:11699): (serine incorporator 3) Predicted to enable L-serine transmembrane transporter activity. Involved in defense response to virus; detection of virus; and innate immune response. Predicted to be located in Golgi apparatus. Predicted to be active in membrane. [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	UniProt
SERINC3	NM_006811.4	c.1314C>G	p.Ser438Arg	missense_variant	10/10	ENST00000342374.5
SERINC3	NM_198941.3	c.1314C>G	p.Ser438Arg	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5	c.1314C>G	p.Ser438Arg	missense_variant	10/10	1	NM_006811.4	P1
SERINC3	ENST00000255175.5	c.1314C>G	p.Ser438Arg	missense_variant	10/11	5		P1
SERINC3	ENST00000411544.5	c.531C>G	p.Ser177Arg	missense_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 30, 2022

The c.1314C>G (p.S438R) alteration is located in exon 10 (coding exon 10) of the SERINC3 gene. This alteration results from a C to G substitution at nucleotide position 1314, causing the serine (S) at amino acid position 438 to be replaced by an arginine (R). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D;.
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.96	.;D;D
Vest4		0.34, 0.20
MutPred		0.71		.;Gain of MoRF binding (P = 0.023);Gain of MoRF binding (P = 0.023);
MVP		0.27
MPC		0.42
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.53
gMVP		0.68

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: chr20-43129045;