chr7-150284838-T-C

Variant names:

• chr7-150284838-T-C
• rs542899681
• NM_001164458.2:c.479A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164458.2(ACTR3C):​c.479A>G​(p.Asn160Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. N160I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACTR3C NM_001164458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

Genes affected

ACTR3C (HGNC:37282): (actin related protein 3C) Predicted to enable ATP binding activity. Predicted to contribute to actin filament binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2396352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2	c.479A>G	p.Asn160Ser	missense_variant	Exon 6 of 8	ENST00000683684.1	NP_001157930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1	c.479A>G	p.Asn160Ser	missense_variant	Exon 6 of 8		NM_001164458.2	ENSP00000507618.1
ACTR3C	ENST00000252071.8	c.479A>G	p.Asn160Ser	missense_variant	Exon 6 of 8	1		ENSP00000252071.4
ACTR3C	ENST00000478393.5	c.473A>G	p.Asn158Ser	missense_variant	Exon 5 of 6	1		ENSP00000417426.1
ACTR3C	ENST00000539352.5	c.479A>G	p.Asn160Ser	missense_variant	Exon 5 of 5	5		ENSP00000440990.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457148 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724754

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 84958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110318

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0015	.;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.025	.;N;.
PhyloP100		5.6
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.92	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.99	.;D;.
Vest4		0.49, 0.50
MutPred		0.43		.;Gain of glycosylation at N160 (P = 0.0117);Gain of glycosylation at N160 (P = 0.0117);
MVP		0.22
MPC		0.33
ClinPred		0.76	D
GERP RS		2.2
Varity_R		0.090
gMVP		0.36
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs542899681; hg19: chr7-149981927;