5-10236506-G-A

Variant names:

• chr5-10236506-G-A
• NM_199133.4:c.416C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199133.4(ATPSCKMT):​c.416C>T​(p.Ala139Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ATPSCKMT NM_199133.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.72

Genes affected

ATPSCKMT (HGNC:27029): (ATP synthase c subunit lysine N-methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation; positive regulation of sensory perception of pain; and regulation of proton transport. Located in mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPSCKMT	NM_199133.4	c.416C>T	p.Ala139Val	missense_variant	Exon 3 of 5	ENST00000511437.6	NP_954584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPSCKMT	ENST00000511437.6	c.416C>T	p.Ala139Val	missense_variant	Exon 3 of 5	1	NM_199133.4	ENSP00000422338.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.416C>T (p.A139V) alteration is located in exon 3 (coding exon 3) of the FAM173B gene. This alteration results from a C to T substitution at nucleotide position 416, causing the alanine (A) at amino acid position 139 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.0098
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.17
Sift	Benign	0.13	T;D
Sift4G	Benign	0.48	T;T
Polyphen		0.57	P;.
Vest4		0.44
MutPred		0.46		Gain of methylation at K140 (P = 0.0367);Gain of methylation at K140 (P = 0.0367);
MVP		0.17
MPC		0.36
ClinPred		0.76	D
GERP RS		4.4
Varity_R		0.063
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 16

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: chr5-10236618;