NM_144698.5:c.2059A>G

Variant names:

• chr1-145872710-T-C
• rs1653886234
• NM_144698.5:c.2059A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144698.5(ANKRD35):​c.2059A>G​(p.Thr687Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ANKRD35 NM_144698.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.150
• Publications: 0 publications found

Genes affected

ANKRD35 (HGNC:26323): (ankyrin repeat domain 35)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12879622).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144698.5. 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
	ANKRD35	NM_144698.5	MANE Select	c.2059A>G	p.Thr687Ala	missense	Exon 10 of 14	NP_653299.4
	ANKRD35	NM_001280799.2		c.1789A>G	p.Thr597Ala	missense	Exon 8 of 12	NP_001267728.1	F6XZD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD35	ENST00000355594.9	TSL:2 MANE Select	c.2059A>G	p.Thr687Ala	missense	Exon 10 of 14	ENSP00000347802.4	Q8N283-1
	ANKRD35	ENST00000948349.1		c.2059A>G	p.Thr687Ala	missense	Exon 11 of 15	ENSP00000618408.1
	ANKRD35	ENST00000544626.2	TSL:5	c.1789A>G	p.Thr597Ala	missense	Exon 8 of 12	ENSP00000442671.2	F6XZD3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461826 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.030	T
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.13	T
PhyloP100		0.15
PROVEAN	Benign	-0.50	N
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.53	T
Vest4		0.16
gMVP		0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1653886234; hg19: chr1-145562371;