chr1-31424845-C-T

Variant names:

• chr1-31424845-C-T
• rs183001614
• NM_178865.5:c.364C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178865.5(SERINC2):​c.364C>T​(p.Arg122Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,611,598 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R122Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (34 hom.)
• Consequence: SERINC2 NM_178865.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06
• Publications: 10 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019129515).
• BP6: Variant 1-31424845-C-T is Benign according to our data. Variant chr1-31424845-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2638601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.364C>T	p.Arg122Trp	missense	Exon 3 of 10	NP_849196.2	Q96SA4-1
	SERINC2	NM_001199038.2		c.391C>T	p.Arg131Trp	missense	Exon 4 of 11	NP_001185967.1	Q96SA4-4
	SERINC2	NM_001199037.2		c.376C>T	p.Arg126Trp	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.364C>T	p.Arg122Trp	missense	Exon 3 of 10	ENSP00000362813.3	Q96SA4-1
	SERINC2	ENST00000851492.1		c.364C>T	p.Arg122Trp	missense	Exon 3 of 11	ENSP00000521551.1
	SERINC2	ENST00000851493.1		c.364C>T	p.Arg122Trp	missense	Exon 3 of 11	ENSP00000521552.1

Frequencies

GnomAD3 genomes AF: 0.00429 AC: 653 AN: 152106 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00800

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00402 AC: 959 AN: 238622 AF XY: 0.00408

Gnomad AFR exome AF: 0.00134

Gnomad AMR exome AF: 0.000646

Gnomad ASJ exome AF: 0.00401

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00265

Gnomad NFE exome AF: 0.00746

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00610 AC: 8898 AN: 1459374 Hom.: 34 Cov.: 33 AF XY: 0.00609 AC XY: 4422 AN XY: 725892

African (AFR) AF: 0.000747 AC: 25 AN: 33460

American (AMR) AF: 0.000606 AC: 27 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00429 AC: 112 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86040

European-Finnish (FIN) AF: 0.00330 AC: 172 AN: 52082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00750 AC: 8340 AN: 1111456

Other (OTH) AF: 0.00367 AC: 221 AN: 60270

GnomAD4 genome AF: 0.00429 AC: 653 AN: 152224 Hom.: 4 Cov.: 32 AF XY: 0.00382 AC XY: 284 AN XY: 74422

African (AFR) AF: 0.00159 AC: 66 AN: 41538

American (AMR) AF: 0.000458 AC: 7 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00800 AC: 544 AN: 67990

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

Alfa AF: 0.00616 Hom.: 9

Bravo AF: 0.00374

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00208 AC: 9

ESP6500EA AF: 0.00790 AC: 67

ExAC AF: 0.00392 AC: 473

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.073	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.29
MVP		0.41
MPC		0.098
ClinPred		0.047	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.56
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs183001614; hg19: chr1-31897692; COSMIC: COSV107485988;