2-224379827-A-C

Variant names:

• chr2-224379827-A-C
• NM_001122779.2:c.1114T>G

Variant summary

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

The NM_001122779.2(FAM124B):​c.1114T>G​(p.Ser372Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM124B NM_001122779.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118

Genes affected

FAM124B (HGNC:26224): (family with sequence similarity 124 member B) Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034525186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM124B	NM_001122779.2	c.1114T>G	p.Ser372Ala	missense_variant	Exon 2 of 2	ENST00000409685.4	NP_001116251.1
FAM124B	NM_024785.3	c.*420T>G		3_prime_UTR_variant	Exon 3 of 3		NP_079061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM124B	ENST00000409685.4	c.1114T>G	p.Ser372Ala	missense_variant	Exon 2 of 2	2	NM_001122779.2	ENSP00000386895.3
FAM124B	ENST00000389874	c.*420T>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000374524.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114T>G (p.S372A) alteration is located in exon 2 (coding exon 2) of the FAM124B gene. This alteration results from a T to G substitution at nucleotide position 1114, causing the serine (S) at amino acid position 372 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.42
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Sift4G	Benign	0.17	T
Polyphen		0.021	B
Vest4		0.083
MutPred		0.20		Loss of disorder (P = 0.0796);
MVP		0.29
MPC		0.092
ClinPred		0.072	T
GERP RS		-0.64
Varity_R		0.051
gMVP		0.20

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: chr2-225244544;