chr16-55566926-C-G

Variant names:

• chr16-55566926-C-G
• rs777300399
• NM_032330.3:c.170C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032330.3(CAPNS2):​c.170C>G​(p.Thr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T57I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPNS2 NM_032330.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00
• Publications: 0 publications found

Genes affected

CAPNS2 (HGNC:16371): (calpain small subunit 2) Enables calcium-dependent cysteine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LPCAT2 (HGNC:26032): (lysophosphatidylcholine acyltransferase 2) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded enzyme may function in two ways: to catalyze the biosynthesis of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) from 1-O-alkyl-sn-glycero-3-phosphocholine, and to catalyze the synthesis of glycerophospholipid precursors from arachidonyl-CoA and lysophosphatidylcholine. The encoded protein may function in membrane biogenesis and production of platelet-activating factor in inflammatory cells. The enzyme may localize to the endoplasmic reticulum and the Golgi. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040212125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032330.3. 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
	CAPNS2	NM_032330.3	MANE Select	c.170C>G	p.Thr57Ser	missense	Exon 1 of 1	NP_115706.1	Q96L46
	LPCAT2	NM_017839.5	MANE Select	c.1216-7705C>G		intron	N/A	NP_060309.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPNS2	ENST00000457326.3	TSL:6 MANE Select	c.170C>G	p.Thr57Ser	missense	Exon 1 of 1	ENSP00000400882.2	Q96L46
	LPCAT2	ENST00000262134.10	TSL:1 MANE Select	c.1216-7705C>G		intron	N/A	ENSP00000262134.5	Q7L5N7-1
	LPCAT2	ENST00000566915.5	TSL:1	n.1298-7705C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.023	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.034
Sift	Benign	0.38	T
Sift4G	Benign	0.35	T
Polyphen		0.011	B
Vest4		0.062
MutPred		0.27		Gain of disorder (P = 0.0638)
MVP		0.35
MPC		0.12
ClinPred		0.13	T
GERP RS		5.7
PromoterAI		-0.017	Neutral
Varity_R		0.081
gMVP		0.13

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: rs777300399; hg19: chr16-55600838;