rs747135256

Variant names:

• chr2-230865053-G-A
• rs747135256
• NM_030926.6:c.28G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-230865053-G-A
• chr2-230865053-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030926.6(ITM2C):​c.28G>A​(p.Val10Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,374,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ITM2C NM_030926.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

Genes affected

ITM2C (HGNC:6175): (integral membrane protein 2C) Enables amyloid-beta binding activity. Involved in negative regulation of neuron projection development and neuron differentiation. Located in several cellular components, including Golgi apparatus; lysosome; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3123793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITM2C	NM_030926.6	c.28G>A	p.Val10Met	missense_variant	Exon 1 of 6	ENST00000326427.11	NP_112188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITM2C	ENST00000326427.11	c.28G>A	p.Val10Met	missense_variant	Exon 1 of 6	1	NM_030926.6	ENSP00000322730.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000291 AC: 4 AN: 1374054 Hom.: 0 Cov.: 30 AF XY: 0.00000295 AC XY: 2 AN XY: 677020

Gnomad4 AFR exome AF: 0.0000344

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000282

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000151

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.1	.;L;L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.030	N;N;N;N
REVEL	Benign	0.077
Sift	Uncertain	0.027	D;D;D;D
Sift4G	Uncertain	0.039	D;T;T;T
Polyphen		1.0, 0.86	.;D;P;D
Vest4		0.32, 0.45, 0.39
MutPred		0.23		Gain of MoRF binding (P = 0.0686);Gain of MoRF binding (P = 0.0686);Gain of MoRF binding (P = 0.0686);Gain of MoRF binding (P = 0.0686);
MVP		0.54
MPC		0.76
ClinPred		0.83	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.074
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs747135256; hg19: chr2-231729768;