Variant 5-10227466-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_199133.4(ATPSCKMT):c.677A>C(p.His226Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ATPSCKMT
NM_199133.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.39

Variant links:

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]

ATPSCKMT links:

ATPSCKMT (HGNC:):

ATPSCKMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.05938831).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATPSCKMT	NM_199133.4 linkuse as main transcript	c.677A>C	p.His226Pro	missense_variant	5/5	ENST00000511437.6	NP_954584.2	Q6P4H8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATPSCKMT	ENST00000511437.6 linkuse as main transcript	c.677A>C	p.His226Pro	missense_variant	5/5	1	NM_199133.4	ENSP00000422338.1	Q6P4H8-1
ATPSCKMT	ENST00000510047.5 linkuse as main transcript	c.626A>C	p.His209Pro	missense_variant	4/4	2		ENSP00000420876.1	Q6P4H8-2
ATPSCKMT	ENST00000280330.12 linkuse as main transcript	c.185A>C	p.His62Pro	missense_variant	6/6	2		ENSP00000280330.8	J3KN90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249536

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135390

show subpopulations

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 SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.677A>C (p.H226P) alteration is located in exon 5 (coding exon 5) of the FAM173B gene. This alteration results from a A to C substitution at nucleotide position 677, causing the histidine (H) at amino acid position 226 to be replaced by a proline (P). 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

0.053

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0030

DANN

Benign

0.69

DEOGEN2

Benign

0.0029

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.32

T;T;T

M_CAP

Benign

0.00064

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.067

Sift

Benign

0.056

T;T;T

Sift4G

Uncertain

0.054

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.071

MutPred

0.40

.;Gain of loop (P = 0.0166);.;

MVP

0.067

MPC

0.12

ClinPred

0.034

GERP RS

-7.3

Varity_R

0.33

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over