5-80143682-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174072.3(SERINC5):​c.1367C>G​(p.Thr456Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict 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. T456I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SERINC5 NM_001174072.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13847473).

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>G	p.Thr456Ser	missense	Exon 12 of 12	NP_001167543.1	Q86VE9-4
	SERINC5	NM_178276.7		c.1238+2408C>G		intron	N/A	NP_840060.1	Q86VE9-1
	SERINC5	NM_001174071.3		c.1238+2408C>G		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>G	p.Thr456Ser	missense	Exon 12 of 12	ENSP00000426237.3	Q86VE9-4
	SERINC5	ENST00000509193.6	TSL:1	c.1238+2408C>G		intron	N/A	ENSP00000426134.2	Q86VE9-2
	SERINC5	ENST00000867105.1		c.1361C>G	p.Thr454Ser	missense	Exon 12 of 12	ENSP00000537164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.52
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.7
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.72	T
Vest4		0.025
MVP		0.19
ClinPred		0.27	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.16
Mutation Taster		=91/9	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;