chr20-44501114-C-A

Position:

• chr20-44501114-C-A

Variant summary

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

The NM_006811.4(SERINC3):​c.1242G>T​(p.Leu414Phe) 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: 0.145

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.1242G>T	p.Leu414Phe	missense_variant	9/10	ENST00000342374.5
SERINC3	NM_198941.3	c.1242G>T	p.Leu414Phe	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5	c.1242G>T	p.Leu414Phe	missense_variant	9/10	1	NM_006811.4	P1
SERINC3	ENST00000255175.5	c.1242G>T	p.Leu414Phe	missense_variant	9/11	5		P1
SERINC3	ENST00000411544.5	c.459G>T	p.Leu153Phe	missense_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 28, 2023

The c.1242G>T (p.L414F) alteration is located in exon 9 (coding exon 9) of the SERINC3 gene. This alteration results from a G to T substitution at nucleotide position 1242, causing the leucine (L) at amino acid position 414 to be replaced by a phenylalanine (F). 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	0.095
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.88	D;D;.
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Pathogenic	3.8	.;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.99	.;D;D
Vest4		0.49
MutPred		0.83		.;Loss of catalytic residue at L414 (P = 0.0166);Loss of catalytic residue at L414 (P = 0.0166);
MVP		0.43
MPC		0.42
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.22
gMVP		0.63

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: chr20-43129755;