1-145872354-C-T

Variant names:

• chr1-145872354-C-T
• rs369201218
• NM_144698.5:c.2415G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP3 BP7

The NM_144698.5(ANKRD35):​c.2415G>A​(p.Gln805Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD35 NM_144698.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 1 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
• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.15
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.

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.2415G>A	p.Gln805Gln	synonymous	Exon 10 of 14	NP_653299.4
	ANKRD35	NM_001280799.2		c.2145G>A	p.Gln715Gln	synonymous	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.2415G>A	p.Gln805Gln	synonymous	Exon 10 of 14	ENSP00000347802.4	Q8N283-1
	ANKRD35	ENST00000948349.1		c.2415G>A	p.Gln805Gln	synonymous	Exon 11 of 15	ENSP00000618408.1
	ANKRD35	ENST00000544626.2	TSL:5	c.2145G>A	p.Gln715Gln	synonymous	Exon 8 of 12	ENSP00000442671.2	F6XZD3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 96

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		1.7
Mutation Taster		=58/142	disease causing (fs/PTC)

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: rs369201218; hg19: chr1-145562727;