rs200658616

Variant names:

• chr5-10227599-G-A
• rs200658616
• NM_199133.4:c.544C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-10227599-G-A
• chr5-10227599-G-C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_199133.4(ATPSCKMT):​c.544C>T​(p.Arg182*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,614,160 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (20 hom.)
• Consequence: ATPSCKMT NM_199133.4 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.653
• Publications: 14 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 5-10227599-G-A is Benign according to our data. Variant chr5-10227599-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2655295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199133.4. 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
	ATPSCKMT	NM_199133.4	MANE Select	c.544C>T	p.Arg182*	stop_gained	Exon 5 of 5	NP_954584.2	Q6P4H8-1
	ATPSCKMT	NM_001258388.2		c.493C>T	p.Arg165*	stop_gained	Exon 4 of 4	NP_001245317.1	Q6P4H8-2
	ATPSCKMT	NM_001258389.2		c.*23C>T		3_prime_UTR	Exon 5 of 5	NP_001245318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	ENST00000511437.6	TSL:1 MANE Select	c.544C>T	p.Arg182*	stop_gained	Exon 5 of 5	ENSP00000422338.1	Q6P4H8-1
	ATPSCKMT	ENST00000932928.1		c.535C>T	p.Arg179*	stop_gained	Exon 5 of 5	ENSP00000602987.1
	ATPSCKMT	ENST00000510047.5	TSL:2	c.493C>T	p.Arg165*	stop_gained	Exon 4 of 4	ENSP00000420876.1	Q6P4H8-2

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 511 AN: 152154 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00934

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00460

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00339 AC: 846 AN: 249532 AF XY: 0.00339

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.00508

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00389 AC: 5683 AN: 1461888 Hom.: 20 Cov.: 35 AF XY: 0.00379 AC XY: 2758 AN XY: 727244

African (AFR) AF: 0.00119 AC: 40 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86258

European-Finnish (FIN) AF: 0.00844 AC: 451 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00445 AC: 4943 AN: 1112008

Other (OTH) AF: 0.00288 AC: 174 AN: 60396

GnomAD4 genome AF: 0.00336 AC: 511 AN: 152272 Hom.: 3 Cov.: 33 AF XY: 0.00325 AC XY: 242 AN XY: 74446

African (AFR) AF: 0.00142 AC: 59 AN: 41552

American (AMR) AF: 0.00190 AC: 29 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00934 AC: 99 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00460 AC: 313 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00379 Hom.: 4

Bravo AF: 0.00276

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.00102 AC: 4

ESP6500EA AF: 0.00505 AC: 42

ExAC AF: 0.00376 AC: 455

EpiCase AF: 0.00409

EpiControl AF: 0.00338

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	35
DANN	Benign	0.92
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.36	N
PhyloP100		0.65
Vest4		0.17
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=130/70	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200658616; hg19: chr5-10227711; COSMIC: COSV104600219; COSMIC: COSV104600219;