NM_001174072.3:c.1348G>T

Variant names:

• chr5-80143701-C-A
• rs537411704
• NM_001174072.3:c.1348G>T

Variant summary

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

The NM_001174072.3(SERINC5):​c.1348G>T​(p.Ala450Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A450T) 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: 5.01
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1348G>T	p.Ala450Ser	missense	Exon 12 of 12	NP_001167543.1	Q86VE9-4
	SERINC5	NM_178276.7		c.1238+2389G>T		intron	N/A	NP_840060.1	Q86VE9-1
	SERINC5	NM_001174071.3		c.1238+2389G>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.1348G>T	p.Ala450Ser	missense	Exon 12 of 12	ENSP00000426237.3	Q86VE9-4
	SERINC5	ENST00000509193.6	TSL:1	c.1238+2389G>T		intron	N/A	ENSP00000426134.2	Q86VE9-2
	SERINC5	ENST00000867105.1		c.1342G>T	p.Ala448Ser	missense	Exon 12 of 12	ENSP00000537164.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000746 AC: 1 AN: 134088 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383818 Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1 AN XY: 682852

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: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078842

Other (OTH) AF: 0.00 AC: 0 AN: 57918

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.70	T
PhyloP100		5.0
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.061	T
Vest4		0.43
MVP		0.23
ClinPred		0.89	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.63
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs537411704; hg19: chr5-79439524;