5-80143682-G-A

Variant names:

• chr5-80143682-G-A
• rs1183259553
• NM_001174072.3:c.1367C>T

Variant summary

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

The NM_001174072.3(SERINC5):​c.1367C>T​(p.Thr456Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 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)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SERINC5 NM_001174072.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.72
• 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=0.26768774).

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.1367C>T	p.Thr456Ile	missense	Exon 12 of 12	NP_001167543.1	Q86VE9-4
	SERINC5	NM_178276.7		c.1238+2408C>T		intron	N/A	NP_840060.1	Q86VE9-1
	SERINC5	NM_001174071.3		c.1238+2408C>T		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.1367C>T	p.Thr456Ile	missense	Exon 12 of 12	ENSP00000426237.3	Q86VE9-4
	SERINC5	ENST00000509193.6	TSL:1	c.1238+2408C>T		intron	N/A	ENSP00000426134.2	Q86VE9-2
	SERINC5	ENST00000867105.1		c.1361C>T	p.Thr454Ile	missense	Exon 12 of 12	ENSP00000537164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383820 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 682852

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 25182

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078856

Other (OTH) AF: 0.0000173 AC: 1 AN: 57924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.98
Eigen	Benign	0.0081
Eigen_PC	Benign	0.0021
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.7
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.13	T
Vest4		0.16
MVP		0.28
ClinPred		0.77	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.35
Mutation Taster		=82/18	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: rs1183259553; hg19: chr5-79439505; COSMIC: COSV101549136;