2-224401446-G-T

Variant names:

• chr2-224401446-G-T
• rs149759174
• NM_001122779.2:c.323C>A

Variant summary

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

The NM_001122779.2(FAM124B):​c.323C>A​(p.Pro108His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P108L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM124B NM_001122779.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122779.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM124B	NM_001122779.2	MANE Select	c.323C>A	p.Pro108His	missense	Exon 1 of 2	NP_001116251.1	Q9H5Z6-1
	FAM124B	NM_024785.3		c.323C>A	p.Pro108His	missense	Exon 1 of 3	NP_079061.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM124B	ENST00000409685.4	TSL:2 MANE Select	c.323C>A	p.Pro108His	missense	Exon 1 of 2	ENSP00000386895.3	Q9H5Z6-1
	FAM124B	ENST00000243806.2	TSL:1	c.323C>A	p.Pro108His	missense	Exon 1 of 2	ENSP00000243806.2	Q9H5Z6-2
	FAM124B	ENST00000389874.3	TSL:1	c.323C>A	p.Pro108His	missense	Exon 1 of 3	ENSP00000374524.3	Q9H5Z6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250848 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.6
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.72		Gain of relative solvent accessibility (P = 0.09)
MVP		0.83
MPC		0.56
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.87
gMVP		0.54
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs149759174; hg19: chr2-225266163;