5-80166446-C-T

Variant names:

• chr5-80166446-C-T
• rs745502617
• NM_001174072.3:c.796G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174072.3(SERINC5):​c.796G>A​(p.Val266Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,595,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SERINC5 NM_001174072.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

Genes affected

SERINC5 (HGNC:18825): (serine incorporator 5) Predicted to enable L-serine transmembrane transporter activity. Involved in defense response to virus; detection of virus; and innate immune response. Located in several cellular components, including centrosome; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13577157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERINC5	NM_001174072.3	c.796G>A	p.Val266Ile	missense_variant	Exon 7 of 12	ENST00000507668.7	NP_001167543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERINC5	ENST00000507668.7	c.796G>A	p.Val266Ile	missense_variant	Exon 7 of 12	2	NM_001174072.3	ENSP00000426237.3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1443494 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 715992

Gnomad4 AFR exome AF: 0.0000603

Gnomad4 AMR exome AF: 0.0000237

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74428

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ExAC AF: 0.0000249 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.796G>A (p.V266I) alteration is located in exon 7 (coding exon 7) of the SERINC5 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the valine (V) at amino acid position 266 to be replaced by an isoleucine (I). 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
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.23
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.12	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.22	N;N
REVEL	Benign	0.060
Sift	Benign	0.66	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.032	B;.
Vest4		0.12
MutPred		0.64		Loss of catalytic residue at V266 (P = 0.0018);Loss of catalytic residue at V266 (P = 0.0018);
MVP		0.17
ClinPred		0.0046	T
GERP RS		5.0
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs745502617; hg19: chr5-79462269;