rs979488558

Variant names:

• chr16-721351-C-T
• rs979488558
• NM_023933.3:c.77C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-721351-C-T
• chr16-721351-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_023933.3(ANTKMT):​c.77C>T​(p.Ala26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,338,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ANTKMT NM_023933.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200
• Publications: 0 publications found

Genes affected

ANTKMT (HGNC:14152): (adenine nucleotide translocase lysine methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.027265728).
• BP6: Variant 16-721351-C-T is Benign according to our data. Variant chr16-721351-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3401643.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023933.3. 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
	ANTKMT	NM_023933.3	MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 5	NP_076422.1	Q9BQD7
	ANTKMT	NM_001271285.2		c.77C>T	p.Ala26Val	missense	Exon 1 of 4	NP_001258214.1	J3KMW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANTKMT	ENST00000569529.6	TSL:1 MANE Select	c.77C>T	p.Ala26Val	missense	Exon 1 of 5	ENSP00000454380.1	Q9BQD7
	ANTKMT	ENST00000853259.1		c.77C>T	p.Ala26Val	missense	Exon 1 of 5	ENSP00000523318.1
	ANTKMT	ENST00000853260.1		c.77C>T	p.Ala26Val	missense	Exon 1 of 5	ENSP00000523319.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000405 AC: 1 AN: 24676 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000337 AC: 4 AN: 1186664 Hom.: 0 Cov.: 33 AF XY: 0.00000173 AC XY: 1 AN XY: 579196

African (AFR) AF: 0.00 AC: 0 AN: 23736

American (AMR) AF: 0.000299 AC: 4 AN: 13390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17012

East Asian (EAS) AF: 0.00 AC: 0 AN: 25978

South Asian (SAS) AF: 0.00 AC: 0 AN: 50060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 978020

Other (OTH) AF: 0.00 AC: 0 AN: 47618

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151812 Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1 AN XY: 74154

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.8
DANN	Benign	0.93
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.35	N
PhyloP100		0.020
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.054
Sift	Benign	0.95	T
Sift4G	Benign	0.94	T
Polyphen		0.0030	B
Vest4		0.079
MutPred		0.44		Loss of helix (P = 0.0068)
MVP		0.048
MPC		0.078
ClinPred		0.033	T
GERP RS		-4.3
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.039
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs979488558; hg19: chr16-771351;