12-50396337-T-C

Position:

• chr12-50396337-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001145475.3(FAM186A):​c.148A>G​(p.Ile50Val) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166

Genes affected

FAM186A (HGNC:26980): (family with sequence similarity 186 member A)

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031828612).
• BP6: Variant 12-50396337-T-C is Benign according to our data. Variant chr12-50396337-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2604839.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.148A>G	p.Ile50Val	missense_variant	1/8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.148A>G	p.Ile50Val	missense_variant	1/8	5	NM_001145475.3	ENSP00000329995	A2
FAM186A	ENST00000543111.5	c.148A>G	p.Ile50Val	missense_variant	1/8	5		ENSP00000441337	A2
LARP4	ENST00000550522.5	c.-193+3749T>C		intron_variant		4		ENSP00000448180

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
DANN	Benign	0.57
DEOGEN2	Benign	0.0026	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.014	.;B
Vest4		0.046
MutPred		0.19		Loss of catalytic residue at I50 (P = 0.0368);Loss of catalytic residue at I50 (P = 0.0368);
MVP		0.030
ClinPred		0.039	T
GERP RS		0.30
Varity_R		0.017
gMVP		0.0091

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50790120;