2-97158601-T-C

Variant names:

• chr2-97158601-T-C
• rs199723612
• NM_001354587.1:c.1335T>C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001354587.1(ANKRD36):​c.1335T>C​(p.Cys445Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,536,038 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00058 (5 hom.)
• Consequence: ANKRD36 NM_001354587.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.475

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-97158601-T-C is Benign according to our data. Variant chr2-97158601-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651161.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.475 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36	ENST00000420699.9	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76	5	NM_001354587.1	ENSP00000391950.4
ANKRD36	ENST00000461153.7	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 75	5		ENSP00000419530.3
ANKRD36	ENST00000652721.1	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76			ENSP00000498611.1

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151658 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.000615 AC: 89 AN: 144680 Hom.: 1 AF XY: 0.000688 AC XY: 53 AN XY: 77050

Gnomad AFR exome AF: 0.000258

Gnomad AMR exome AF: 0.000489

Gnomad ASJ exome AF: 0.000712

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000484

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000841

Gnomad OTH exome AF: 0.00186

GnomAD4 exome AF: 0.000579 AC: 801 AN: 1384264 Hom.: 5 Cov.: 30 AF XY: 0.000609 AC XY: 416 AN XY: 683050

Gnomad4 AFR exome AF: 0.000158

Gnomad4 AMR exome AF: 0.000505

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000442

Gnomad4 FIN exome AF: 0.0000286

Gnomad4 NFE exome AF: 0.000616

Gnomad4 OTH exome AF: 0.000657

GnomAD4 genome AF: 0.000323 AC: 49 AN: 151774 Hom.: 0 Cov.: 33 AF XY: 0.000270 AC XY: 20 AN XY: 74126

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000427 Hom.: 1

Bravo AF: 0.000321

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.5
DANN	Benign	0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs199723612; hg19: chr2-97824338;