19-36010614-C-T

Variant names:

• chr19-36010614-C-T
• NM_032878.5:c.406G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032878.5(ALKBH6):​c.406G>A​(p.Asp136Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ALKBH6 NM_032878.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.65

Genes affected

ALKBH6 (HGNC:28243): (alkB homolog 6) Predicted to enable dioxygenase activity and metal ion binding activity. Located in focal adhesion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000248101 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH6	NM_032878.5	c.406G>A	p.Asp136Asn	missense_variant	Exon 6 of 7	ENST00000378875.8	NP_116267.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH6	ENST00000378875.8	c.406G>A	p.Asp136Asn	missense_variant	Exon 6 of 7	1	NM_032878.5	ENSP00000368152.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461768 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727196

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.490G>A (p.D164N) alteration is located in exon 6 (coding exon 6) of the ALKBH6 gene. This alteration results from a G to A substitution at nucleotide position 490, causing the aspartic acid (D) at amino acid position 164 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.19
Sift	Benign	0.095	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.82	P;D
Vest4		0.61
MutPred		0.44		.;Loss of phosphorylation at T133 (P = 0.1147);
MVP		0.21
MPC		0.52
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.15
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36501516;