chr1-145872190-T-C

Variant names:

• chr1-145872190-T-C
• rs1653852236
• NM_144698.5:c.2579A>G

Variant summary

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

The NM_144698.5(ANKRD35):​c.2579A>G​(p.Tyr860Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,994 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: 6.9e-7 (0 hom.)
• Consequence: ANKRD35 NM_144698.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.194
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.2579A>G	p.Tyr860Cys	missense	Exon 10 of 14	NP_653299.4
	ANKRD35	NM_001280799.2		c.2309A>G	p.Tyr770Cys	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.2579A>G	p.Tyr860Cys	missense	Exon 10 of 14	ENSP00000347802.4	Q8N283-1
	ANKRD35	ENST00000948349.1		c.2579A>G	p.Tyr860Cys	missense	Exon 11 of 15	ENSP00000618408.1
	ANKRD35	ENST00000544626.2	TSL:5	c.2309A>G	p.Tyr770Cys	missense	Exon 8 of 12	ENSP00000442671.2	F6XZD3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457994 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725214

African (AFR) AF: 0.00 AC: 0 AN: 33278

American (AMR) AF: 0.00 AC: 0 AN: 43810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110524

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.69
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
LIST_S2	Benign	0.85	T
MetaRNN	Uncertain	0.68	D
PhyloP100		0.19
PROVEAN	Uncertain	-3.4	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.047	D
Vest4		0.60
gMVP		0.90

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: rs1653852236; hg19: chr1-145562891;