1-31424687-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_178865.5(SERINC2):​c.206C>A​(p.Pro69His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,444,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P69L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SERINC2 NM_178865.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

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>A	p.Pro69His	missense	Exon 3 of 10	NP_849196.2	Q96SA4-1
	SERINC2	NM_001199038.2		c.233C>A	p.Pro78His	missense	Exon 4 of 11	NP_001185967.1	Q96SA4-4
	SERINC2	NM_001199037.2		c.218C>A	p.Pro73His	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>A	p.Pro69His	missense	Exon 3 of 10	ENSP00000362813.3	Q96SA4-1
	SERINC2	ENST00000851492.1		c.206C>A	p.Pro69His	missense	Exon 3 of 11	ENSP00000521551.1
	SERINC2	ENST00000851493.1		c.206C>A	p.Pro69His	missense	Exon 3 of 11	ENSP00000521552.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1444024 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 52072

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

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103592

Other (OTH) AF: 0.00 AC: 0 AN: 59650

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.047	D
Polyphen		0.96	D
Vest4		0.91
MutPred		0.67		Loss of ubiquitination at K67 (P = 0.0724)
MVP		0.31
MPC		0.49
ClinPred		1.0	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.63
Mutation Taster		=37/63	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;