19-36010625-T-G

Variant names:

• chr19-36010625-T-G
• NM_032878.5:c.395A>C

Variant summary

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

The NM_032878.5(ALKBH6):​c.395A>C​(p.His132Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000092 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALKBH6 NM_032878.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74

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.395A>C	p.His132Pro	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.395A>C	p.His132Pro	missense_variant	Exon 6 of 7	1	NM_032878.5	ENSP00000368152.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000924 AC: 135 AN: 1460918 Hom.: 0 Cov.: 32 AF XY: 0.0000798 AC XY: 58 AN XY: 726770

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.479A>C (p.H160P) alteration is located in exon 6 (coding exon 6) of the ALKBH6 gene. This alteration results from a A to C substitution at nucleotide position 479, causing the histidine (H) at amino acid position 160 to be replaced by a proline (P). 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	0.27
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-8.8	D;D
REVEL	Benign	0.29
Sift	Benign	0.12	T;D
Sift4G	Benign	0.46	T;T
Polyphen		1.0	D;D
Vest4		0.54
MutPred		0.42		.;Loss of catalytic residue at H132 (P = 0.0203);
MVP		0.25
MPC		1.2
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.78

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: chr19-36501527;