chr5-80151081-G-A

Variant names:

• chr5-80151081-G-A
• rs73772260
• NM_001174072.3:c.987-133C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174072.3(SERINC5):​c.987-133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 698,702 control chromosomes in the GnomAD database, including 13,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2847 hom., cov: 33)
  • Exomes 𝑓: 0.19 (10513 hom.)
• Consequence: SERINC5 NM_001174072.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERINC5	NM_001174072.3	c.987-133C>T		intron_variant	Intron 8 of 11	ENST00000507668.7	NP_001167543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERINC5	ENST00000507668.7	c.987-133C>T		intron_variant	Intron 8 of 11	2	NM_001174072.3	ENSP00000426237.3
SERINC5	ENST00000509193.6	c.987-133C>T		intron_variant	Intron 8 of 12	1		ENSP00000426134.2
SERINC5	ENST00000512972.6	n.987-133C>T		intron_variant	Intron 8 of 13	2		ENSP00000421665.2
SERINC5	ENST00000632581.1	n.981-133C>T		intron_variant	Intron 8 of 13	2		ENSP00000488864.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29056 AN: 152024 Hom.: 2843 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.189 AC: 103106 AN: 546560 Hom.: 10513 AF XY: 0.194 AC XY: 56991 AN XY: 294126

African (AFR) AF: 0.199 AC: 3022 AN: 15184

American (AMR) AF: 0.145 AC: 4344 AN: 29932

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 4006 AN: 17908

East Asian (EAS) AF: 0.0702 AC: 2353 AN: 33500

South Asian (SAS) AF: 0.256 AC: 15332 AN: 59992

European-Finnish (FIN) AF: 0.152 AC: 6029 AN: 39702

Middle Eastern (MID) AF: 0.196 AC: 451 AN: 2302

European-Non Finnish (NFE) AF: 0.194 AC: 61624 AN: 318320

Other (OTH) AF: 0.200 AC: 5945 AN: 29720

GnomAD4 genome AF: 0.191 AC: 29086 AN: 152142 Hom.: 2847 Cov.: 33 AF XY: 0.189 AC XY: 14085 AN XY: 74370

African (AFR) AF: 0.199 AC: 8250 AN: 41512

American (AMR) AF: 0.185 AC: 2825 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.0813 AC: 421 AN: 5178

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10572

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13353 AN: 67988

Other (OTH) AF: 0.209 AC: 440 AN: 2108

Alfa AF: 0.194 Hom.: 373

Bravo AF: 0.190

Asia WGS AF: 0.166 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.85
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs73772260; hg19: chr5-79446904; COSMIC: COSV72597066;