20-44504878-C-A

Position:

• chr20-44504878-C-A

Variant summary

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

The NM_006811.4(SERINC3):​c.797G>T​(p.Arg266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SERINC3 NM_006811.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.729

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.797G>T	p.Arg266Leu	missense_variant	7/10	ENST00000342374.5
SERINC3	NM_198941.3	c.797G>T	p.Arg266Leu	missense_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC3	ENST00000342374.5	c.797G>T	p.Arg266Leu	missense_variant	7/10	1	NM_006811.4	P1
SERINC3	ENST00000255175.5	c.797G>T	p.Arg266Leu	missense_variant	7/11	5		P1
SERINC3	ENST00000411544.5	c.14G>T	p.Arg5Leu	missense_variant	1/5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460670 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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

Dec 12, 2022

The c.797G>T (p.R266L) alteration is located in exon 7 (coding exon 7) of the SERINC3 gene. This alteration results from a G to T substitution at nucleotide position 797, causing the arginine (R) at amino acid position 266 to be replaced by a leucine (L). 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	0.38
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	0.063
Eigen_PC	Benign	-0.083
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.97	D;D;.
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	4.0	.;H;H
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.4	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.73, 0.73
MutPred		0.67		.;Loss of disorder (P = 0.078);Loss of disorder (P = 0.078);
MVP		0.35
MPC		0.38
ClinPred		0.97	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs143381118; hg19: chr20-43133519;