chr6-122452490-A-C

Position:

• chr6-122452490-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020755.4(SERINC1):​c.590-433T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,976 control chromosomes in the GnomAD database, including 22,812 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 0.54 (22812 hom., cov: 32)
• Consequence: SERINC1 NM_020755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

Genes affected

SERINC1 (HGNC:13464): (serine incorporator 1) Predicted to enable protein-macromolecule adaptor activity. Predicted to be involved in several processes, including phosphatidylserine metabolic process; positive regulation of CDP-diacylglycerol-serine O-phosphatidyltransferase activity; and positive regulation of serine C-palmitoyltransferase activity. Predicted to be located in endoplasmic reticulum membrane and plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC1	NM_020755.4	c.590-433T>G		intron_variant		ENST00000339697.5	NP_065806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERINC1	ENST00000339697.5	c.590-433T>G		intron_variant		1	NM_020755.4	ENSP00000342962	P1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82787 AN: 151858 Hom.: 22815 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.542

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.545 AC: 82810 AN: 151976 Hom.: 22812 Cov.: 32 AF XY: 0.548 AC XY: 40726 AN XY: 74286

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.541

Alfa AF: 0.541 Hom.: 2759

Bravo AF: 0.544

Asia WGS AF: 0.569 AC: 1978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1267948; hg19: chr6-122773635; COSMIC: COSV60101751; COSMIC: COSV60101751;