rs782039097

Variant names:

• chr1-31424687-C-T
• rs782039097
• NM_178865.5:c.206C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-31424687-C-T
• chr1-31424687-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_178865.5(SERINC2):​c.206C>T​(p.Pro69Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,596,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: SERINC2 NM_178865.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56
• Publications: 0 publications found

Genes affected

SERINC2 (HGNC:23231): (serine incorporator 2) 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. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178865.5. 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
	SERINC2	NM_178865.5	MANE Select	c.206C>T	p.Pro69Leu	missense	Exon 3 of 10	NP_849196.2	Q96SA4-1
	SERINC2	NM_001199038.2		c.233C>T	p.Pro78Leu	missense	Exon 4 of 11	NP_001185967.1	Q96SA4-4
	SERINC2	NM_001199037.2		c.218C>T	p.Pro73Leu	missense	Exon 3 of 10	NP_001185966.1	Q96SA4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERINC2	ENST00000373709.8	TSL:1 MANE Select	c.206C>T	p.Pro69Leu	missense	Exon 3 of 10	ENSP00000362813.3	Q96SA4-1
	SERINC2	ENST00000851492.1		c.206C>T	p.Pro69Leu	missense	Exon 3 of 11	ENSP00000521551.1
	SERINC2	ENST00000851493.1		c.206C>T	p.Pro69Leu	missense	Exon 3 of 11	ENSP00000521552.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000823 AC: 18 AN: 218672 AF XY: 0.000110

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: 0.000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000202 AC: 292 AN: 1444022 Hom.: 0 Cov.: 33 AF XY: 0.000198 AC XY: 142 AN XY: 716916

African (AFR) AF: 0.00 AC: 0 AN: 33194

American (AMR) AF: 0.00 AC: 0 AN: 41738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25544

East Asian (EAS) AF: 0.00 AC: 0 AN: 38966

South Asian (SAS) AF: 0.00 AC: 0 AN: 83558

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.000250 AC: 276 AN: 1103590

Other (OTH) AF: 0.000251 AC: 15 AN: 59650

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000414 AC: 5

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		0.98	D
Vest4		0.96
MVP		0.26
MPC		0.46
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.70
Mutation Taster		=41/59	disease causing

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: rs782039097; hg19: chr1-31897534;