rs61739327

Variant names:

• chr6-89630727-C-T
• rs61739327
• NM_001242809.2:c.1907C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000339746.9(ANKRD6):​c.1907C>T​(p.Pro636Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,606 control chromosomes in the GnomAD database, including 14,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P636P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.099 (961 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13529 hom.)
• Consequence: ANKRD6 ENST00000339746.9 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.808
• Publications: 18 publications found

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LYRM2 (HGNC:25229): (LYR motif containing 2)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011639893).
• BP6: Variant 6-89630727-C-T is Benign according to our data. Variant chr6-89630727-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060598.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339746.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	NM_001242809.2	MANE Select	c.1907C>T	p.Pro636Leu	missense	Exon 16 of 16	NP_001229738.1
	ANKRD6	NM_001242811.1		c.1907C>T	p.Pro636Leu	missense	Exon 16 of 16	NP_001229740.1
	ANKRD6	NM_014942.4		c.1892C>T	p.Pro631Leu	missense	Exon 16 of 16	NP_055757.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.1907C>T	p.Pro636Leu	missense	Exon 16 of 16	ENSP00000345767.4
	ANKRD6	ENST00000447838.6	TSL:1	c.1892C>T	p.Pro631Leu	missense	Exon 16 of 16	ENSP00000396771.2
	ANKRD6	ENST00000369408.9	TSL:1	c.1802C>T	p.Pro601Leu	missense	Exon 15 of 15	ENSP00000358416.5

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15042 AN: 152172 Hom.: 963 Cov.: 33

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.117 AC: 29158 AN: 248226 AF XY: 0.124

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.0660

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0563

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.132 AC: 193138 AN: 1461316 Hom.: 13529 Cov.: 38 AF XY: 0.135 AC XY: 97779 AN XY: 726920

African (AFR) AF: 0.0206 AC: 691 AN: 33478

American (AMR) AF: 0.0691 AC: 3086 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3046 AN: 26126

East Asian (EAS) AF: 0.0454 AC: 1801 AN: 39690

South Asian (SAS) AF: 0.167 AC: 14396 AN: 86240

European-Finnish (FIN) AF: 0.129 AC: 6894 AN: 53262

Middle Eastern (MID) AF: 0.140 AC: 806 AN: 5766

European-Non Finnish (NFE) AF: 0.139 AC: 154872 AN: 1111708

Other (OTH) AF: 0.125 AC: 7546 AN: 60362

GnomAD4 genome AF: 0.0987 AC: 15030 AN: 152290 Hom.: 961 Cov.: 33 AF XY: 0.0980 AC XY: 7293 AN XY: 74454

African (AFR) AF: 0.0244 AC: 1015 AN: 41578

American (AMR) AF: 0.0875 AC: 1339 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3470

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5190

South Asian (SAS) AF: 0.155 AC: 750 AN: 4828

European-Finnish (FIN) AF: 0.124 AC: 1317 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9551 AN: 68006

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.123 Hom.: 2882

Bravo AF: 0.0928

TwinsUK AF: 0.147 AC: 546

ALSPAC AF: 0.141 AC: 542

ESP6500AA AF: 0.0242 AC: 102

ESP6500EA AF: 0.139 AC: 1177

ExAC AF: 0.120 AC: 14492

Asia WGS AF: 0.103 AC: 359 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.151

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ANKRD6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.81
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.043
Sift	Uncertain	0.029	D
Sift4G	Benign	0.11	T
Polyphen		0.55	P
Vest4		0.062
MPC		0.052
ClinPred		0.028	T
GERP RS		1.6
Varity_R		0.053
gMVP		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs61739327; hg19: chr6-90340446; COSMIC: COSV60231871; COSMIC: COSV60231871;