2-24190522-A-G

Position:

• chr2-24190522-A-G

Variant summary

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

The NM_001040710.3(FAM228A):​c.512A>G​(p.Gln171Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM228A NM_001040710.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.891

Genes affected

FAM228A (HGNC:34418): (family with sequence similarity 228 member A)

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=0.06480336).
• BP6: Variant 2-24190522-A-G is Benign according to our data. Variant chr2-24190522-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2609276.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM228A	NM_001040710.3	c.512A>G	p.Gln171Arg	missense_variant	6/6	ENST00000295150.8	NP_001035800.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM228A	ENST00000295150.8	c.512A>G	p.Gln171Arg	missense_variant	6/6	1	NM_001040710.3	ENSP00000295150.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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 30, 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	0.063
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.016
DANN	Benign	0.32
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.7	N;D
REVEL	Benign	0.083
Sift	Benign	0.26	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0	B;.
Vest4		0.031
MutPred		0.13		Gain of MoRF binding (P = 0.0401);.;
MVP		0.030
MPC		0.057
ClinPred		0.31	T
GERP RS		-5.6
Varity_R		0.051
gMVP		0.019

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: chr2-24413391;