6-89606070-A-T

Position:

• chr6-89606070-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001242809.2(ANKRD6):​c.382A>T​(p.Ile128Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I128V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

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)

LOC124901359 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD6	NM_001242809.2	c.382A>T	p.Ile128Phe	missense_variant	5/16	ENST00000339746.9	NP_001229738.1
LOC124901359	XR_007059673.1	n.206-139T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9	c.382A>T	p.Ile128Phe	missense_variant	5/16	1	NM_001242809.2	ENSP00000345767	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1435712 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 711488

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000836 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	.;T;.;T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.081
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;.;D;T;D;D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M;M;M;.;M;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D;D;D
Polyphen		0.056	B;B;.;.;B;.
Vest4		0.40
MutPred		0.77		Gain of methylation at K129 (P = 0.084);Gain of methylation at K129 (P = 0.084);Gain of methylation at K129 (P = 0.084);Gain of methylation at K129 (P = 0.084);Gain of methylation at K129 (P = 0.084);Gain of methylation at K129 (P = 0.084);
MVP		0.76
MPC		0.11
ClinPred		0.95	D
GERP RS		4.1
Varity_R		0.28
gMVP		0.73

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

Other links and lift over

dbSNP: rs3748085; hg19: chr6-90315789;