18-9254238-C-T

Variant names:

• chr18-9254238-C-T
• rs142598284
• NM_015208.5:c.971C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_015208.5(ANKRD12):​c.971C>T​(p.Pro324Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,589,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: ANKRD12 NM_015208.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 0 publications found

Genes affected

ANKRD12 (HGNC:29135): (ankyrin repeat domain 12) This gene encodes a member of the ankyrin repeats-containing cofactor family. These proteins may inhibit the transcriptional activity of nuclear receptors through the recruitment of histone deacetylases. The encoded protein interacts with p160 coactivators and also represses transcription mediated by the coactivator alteration/deficiency in activation 3 (ADA3). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

ENSG00000265257 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26870364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015208.5. 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
	ANKRD12	NM_015208.5	MANE Select	c.971C>T	p.Pro324Leu	missense	Exon 9 of 13	NP_056023.3
	ANKRD12	NM_001083625.3		c.902C>T	p.Pro301Leu	missense	Exon 8 of 12	NP_001077094.1	Q6UB98-2
	ANKRD12	NM_001204056.1		c.902C>T	p.Pro301Leu	missense	Exon 8 of 12	NP_001190985.1	Q6UB98-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD12	ENST00000262126.9	TSL:1 MANE Select	c.971C>T	p.Pro324Leu	missense	Exon 9 of 13	ENSP00000262126.3	Q6UB98-1
	ANKRD12	ENST00000400020.7	TSL:1	c.902C>T	p.Pro301Leu	missense	Exon 8 of 12	ENSP00000382897.3	Q6UB98-2
	ANKRD12	ENST00000917028.1		c.971C>T	p.Pro324Leu	missense	Exon 9 of 13	ENSP00000587087.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151976 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000118

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000777 AC: 18 AN: 231804 AF XY: 0.0000875

Gnomad AFR exome AF: 0.0000643

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000144

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000180 AC: 259 AN: 1437610 Hom.: 0 Cov.: 31 AF XY: 0.000166 AC XY: 119 AN XY: 714796

African (AFR) AF: 0.0000311 AC: 1 AN: 32108

American (AMR) AF: 0.0000509 AC: 2 AN: 39302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39020

South Asian (SAS) AF: 0.00 AC: 0 AN: 81326

European-Finnish (FIN) AF: 0.000209 AC: 11 AN: 52592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.000209 AC: 231 AN: 1103328

Other (OTH) AF: 0.000236 AC: 14 AN: 59308

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151976 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67972

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.0000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.24
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Benign	0.88
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.46
MVP		0.77
ClinPred		0.16	T
GERP RS		5.4
Varity_R		0.69
gMVP		0.45
Mutation Taster		=81/19	polymorphism

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: rs142598284; hg19: chr18-9254236;