chr20-44510010-A-G

Position:

• chr20-44510010-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006811.4(SERINC3):​c.494T>C​(p.Met165Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3247211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC3	NM_006811.4	c.494T>C	p.Met165Thr	missense_variant	5/10	ENST00000342374.5
SERINC3	NM_198941.3	c.494T>C	p.Met165Thr	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5	c.494T>C	p.Met165Thr	missense_variant	5/10	1	NM_006811.4	P1
SERINC3	ENST00000255175.5	c.494T>C	p.Met165Thr	missense_variant	5/11	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Feb 06, 2024

The c.494T>C (p.M165T) alteration is located in exon 5 (coding exon 5) of the SERINC3 gene. This alteration results from a T to C substitution at nucleotide position 494, causing the methionine (M) at amino acid position 165 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.10
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.0010	B;B
Vest4		0.39
MutPred		0.63		Gain of catalytic residue at M165 (P = 0.0211);Gain of catalytic residue at M165 (P = 0.0211);
MVP		0.068
MPC		0.092
ClinPred		0.81	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.39

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: chr20-43138651; COSMIC: COSV54856982; COSMIC: COSV54856982;