chr19-17282085-G-T

Variant names:

• chr19-17282085-G-T
• rs8100241
• NM_152363.6:c.91G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152363.6(ANKLE1):​c.91G>T​(p.Ala31Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ANKLE1 NM_152363.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• Publications: 90 publications found

Genes affected

ANKLE1 (HGNC:26812): (ankyrin repeat and LEM domain containing 1) Enables endonuclease activity. Involved in positive regulation of response to DNA damage stimulus and protein export from nucleus. Located in cytosol and nucleoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269307 (HGNC:):

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37320215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKLE1	NM_152363.6	c.91G>T	p.Ala31Ser	missense_variant	Exon 2 of 9	ENST00000404085.7	NP_689576.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKLE1	ENST00000404085.7	c.91G>T	p.Ala31Ser	missense_variant	Exon 2 of 9	2	NM_152363.6	ENSP00000384008.3
ENSG00000269307	ENST00000596542.1	n.*424G>T		non_coding_transcript_exon_variant	Exon 8 of 10	2		ENSP00000469159.2
ENSG00000269307	ENST00000596542.1	n.*424G>T		3_prime_UTR_variant	Exon 8 of 10	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T;.
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.028	T
PhyloP100		5.5
PrimateAI	Pathogenic	0.86	D
REVEL	Uncertain	0.33
Sift4G	Uncertain	0.025	D;D
Vest4		0.22
MVP		0.46
MPC		0.68
ClinPred		0.94	D
GERP RS		1.6
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.47
Mutation Taster		=92/8	polymorphism

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: rs8100241; hg19: chr19-17392894;