chr5-80143668-C-G

Variant names:

• chr5-80143668-C-G
• rs1275313774
• NM_001174072.3:c.1381G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001174072.3(SERINC5):​c.1381G>C​(p.Val461Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V461M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SERINC5 NM_001174072.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.70
• Publications: 0 publications found

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]

ENSG00000251675 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28705657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174072.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERINC5	NM_001174072.3	MANE Select	c.1381G>C	p.Val461Leu	missense	Exon 12 of 12	NP_001167543.1	Q86VE9-4
	SERINC5	NM_178276.7		c.1238+2422G>C		intron	N/A	NP_840060.1	Q86VE9-1
	SERINC5	NM_001174071.3		c.1238+2422G>C		intron	N/A	NP_001167542.1	Q86VE9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERINC5	ENST00000507668.7	TSL:2 MANE Select	c.1381G>C	p.Val461Leu	missense	Exon 12 of 12	ENSP00000426237.3	Q86VE9-4
	SERINC5	ENST00000509193.6	TSL:1	c.1238+2422G>C		intron	N/A	ENSP00000426134.2	Q86VE9-2
	SERINC5	ENST00000867105.1		c.1375G>C	p.Val459Leu	missense	Exon 12 of 12	ENSP00000537164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383752 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 682820

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078820

Other (OTH) AF: 0.00 AC: 0 AN: 57914

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.2	T
PhyloP100		6.7
PrimateAI	Uncertain	0.64	T
Sift4G	Pathogenic	0.0	D
Vest4		0.28
MVP		0.26
ClinPred		0.93	D
GERP RS		5.7
gMVP		0.34
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1275313774; hg19: chr5-79439491;