rs8100241

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-17282085-G-A
• chr19-17282085-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152363.6(ANKLE1):​c.91G>A​(p.Ala31Thr) variant causes a missense change. The variant allele was found at a frequency of 0.5 in 1,539,996 control chromosomes in the GnomAD database, including 193,706 homozygotes. 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: 𝑓 0.47 (17095 hom., cov: 34)
  • Exomes 𝑓: 0.50 (176611 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.9503317E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152363.6. 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
	ANKLE1	NM_152363.6	MANE Select	c.91G>A	p.Ala31Thr	missense	Exon 2 of 9	NP_689576.6
	ANKLE1	NM_001278444.2		c.91G>A	p.Ala31Thr	missense	Exon 2 of 8	NP_001265373.2
	ANKLE1	NM_001278443.2		c.58G>A	p.Ala20Thr	missense	Exon 2 of 9	NP_001265372.2	A0A494C092

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKLE1	ENST00000404085.7	TSL:2 MANE Select	c.91G>A	p.Ala31Thr	missense	Exon 2 of 9	ENSP00000384008.3	Q8NAG6-2
	ANKLE1	ENST00000394458.7	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 2 of 9	ENSP00000377971.4	A0A499FJM0
	ENSG00000269307	ENST00000596542.1	TSL:2	n.*424G>A		non_coding_transcript_exon	Exon 8 of 10	ENSP00000469159.2	M0QXG9

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71562 AN: 151974 Hom.: 17080 Cov.: 34

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.466 AC: 63343 AN: 135892 AF XY: 0.470

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.397

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.313

Gnomad FIN exome AF: 0.554

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.476

GnomAD4 exome AF: 0.503 AC: 697696 AN: 1387904 Hom.: 176611 Cov.: 89 AF XY: 0.502 AC XY: 343540 AN XY: 684930

African (AFR) AF: 0.398 AC: 12569 AN: 31564

American (AMR) AF: 0.396 AC: 14139 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 12658 AN: 25156

East Asian (EAS) AF: 0.320 AC: 11438 AN: 35714

South Asian (SAS) AF: 0.472 AC: 37358 AN: 79206

European-Finnish (FIN) AF: 0.558 AC: 21545 AN: 38596

Middle Eastern (MID) AF: 0.503 AC: 2781 AN: 5532

European-Non Finnish (NFE) AF: 0.516 AC: 556338 AN: 1078598

Other (OTH) AF: 0.499 AC: 28870 AN: 57858

GnomAD4 genome AF: 0.471 AC: 71626 AN: 152092 Hom.: 17095 Cov.: 34 AF XY: 0.471 AC XY: 35052 AN XY: 74360

African (AFR) AF: 0.405 AC: 16820 AN: 41492

American (AMR) AF: 0.423 AC: 6465 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3468

East Asian (EAS) AF: 0.318 AC: 1641 AN: 5154

South Asian (SAS) AF: 0.478 AC: 2310 AN: 4834

European-Finnish (FIN) AF: 0.569 AC: 6031 AN: 10594

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35001 AN: 67956

Other (OTH) AF: 0.473 AC: 998 AN: 2112

Alfa AF: 0.499 Hom.: 34507

Bravo AF: 0.457

TwinsUK AF: 0.499 AC: 1850

ALSPAC AF: 0.507 AC: 1954

ESP6500AA AF: 0.366 AC: 1171

ESP6500EA AF: 0.474 AC: 2712

ExAC AF: 0.397 AC: 9415

Asia WGS AF: 0.422 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Benign	0.16
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.00060	T
MetaSVM	Benign	-0.91	T
PhyloP100		5.5
PrimateAI	Pathogenic	0.87	D
REVEL	Uncertain	0.36
Sift4G	Uncertain	0.028	D
Vest4		0.096
MPC		0.70
ClinPred		0.032	T
GERP RS		1.6
PromoterAI		0.00040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.57
Mutation Taster		=97/3	polymorphism (auto)

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; COSMIC: COSV63920011; COSMIC: COSV63920011;