chr1-31424709-C-T

Variant names:

• chr1-31424709-C-T
• rs147664019
• NM_178865.5:c.228C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_178865.5(SERINC2):​c.228C>T​(p.Ala76Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,603,746 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (20 hom.)
• Consequence: SERINC2 NM_178865.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.299
• Publications: 3 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-31424709-C-T is Benign according to our data. Variant chr1-31424709-C-T is described in ClinVar as Benign. ClinVar VariationId is 788760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.299 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 20 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.228C>T	p.Ala76Ala	synonymous	Exon 3 of 10	NP_849196.2	Q96SA4-1
	SERINC2	NM_001199038.2		c.255C>T	p.Ala85Ala	synonymous	Exon 4 of 11	NP_001185967.1	Q96SA4-4
	SERINC2	NM_001199037.2		c.240C>T	p.Ala80Ala	synonymous	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.228C>T	p.Ala76Ala	synonymous	Exon 3 of 10	ENSP00000362813.3	Q96SA4-1
	SERINC2	ENST00000851492.1		c.228C>T	p.Ala76Ala	synonymous	Exon 3 of 11	ENSP00000521551.1
	SERINC2	ENST00000851493.1		c.228C>T	p.Ala76Ala	synonymous	Exon 3 of 11	ENSP00000521552.1

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 397 AN: 152166 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00273 AC: 625 AN: 228804 AF XY: 0.00310

Gnomad AFR exome AF: 0.000484

Gnomad AMR exome AF: 0.000833

Gnomad ASJ exome AF: 0.00412

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.00110

Gnomad NFE exome AF: 0.00381

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00359 AC: 5216 AN: 1451462 Hom.: 20 Cov.: 33 AF XY: 0.00370 AC XY: 2671 AN XY: 721174

African (AFR) AF: 0.00111 AC: 37 AN: 33326

American (AMR) AF: 0.000998 AC: 43 AN: 43076

Ashkenazi Jewish (ASJ) AF: 0.00415 AC: 107 AN: 25808

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39250

South Asian (SAS) AF: 0.00433 AC: 366 AN: 84470

European-Finnish (FIN) AF: 0.00107 AC: 56 AN: 52478

Middle Eastern (MID) AF: 0.00645 AC: 37 AN: 5740

European-Non Finnish (NFE) AF: 0.00389 AC: 4306 AN: 1107394

Other (OTH) AF: 0.00439 AC: 263 AN: 59920

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152284 Hom.: 1 Cov.: 33 AF XY: 0.00234 AC XY: 174 AN XY: 74462

African (AFR) AF: 0.00101 AC: 42 AN: 41552

American (AMR) AF: 0.00216 AC: 33 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4820

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00385 AC: 262 AN: 68008

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00300 Hom.: 1

Bravo AF: 0.00243

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.5
DANN	Benign	0.31
PhyloP100		-0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs147664019; hg19: chr1-31897556;