rs377367109

Variant names:

• chr6-89612325-G-A
• rs377367109
• NM_001242809.2:c.471G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-89612325-G-A
• chr6-89612325-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001242809.2(ANKRD6):​c.471G>A​(p.Thr157Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000725 in 1,566,304 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 Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00076 (0 hom.)
• Consequence: ANKRD6 NM_001242809.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.31
• Publications: 0 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)

LOC124901359 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-89612325-G-A is Benign according to our data. Variant chr6-89612325-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3046684.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. 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
	ANKRD6	NM_001242809.2	MANE Select	c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.471G>A	p.Thr157Thr	synonymous	Exon 6 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes AF: 0.000355 AC: 54 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

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: 0.000661

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000350 AC: 62 AN: 177264 AF XY: 0.000382

Gnomad AFR exome AF: 0.000416

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000156

Gnomad FIN exome AF: 0.000115

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000765 AC: 1081 AN: 1413954 Hom.: 0 Cov.: 31 AF XY: 0.000736 AC XY: 514 AN XY: 698620

African (AFR) AF: 0.000279 AC: 9 AN: 32306

American (AMR) AF: 0.0000530 AC: 2 AN: 37754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.0000539 AC: 2 AN: 37088

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80008

European-Finnish (FIN) AF: 0.0000398 AC: 2 AN: 50314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.000942 AC: 1024 AN: 1086792

Other (OTH) AF: 0.000699 AC: 41 AN: 58672

GnomAD4 genome AF: 0.000354 AC: 54 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74504

African (AFR) AF: 0.000216 AC: 9 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000661 AC: 45 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000686 Hom.: 0

Bravo AF: 0.000329

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.11
DANN	Benign	0.92
PhyloP100		-2.3
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs377367109; hg19: chr6-90322044;