NM_001393982.1:c.2865T>A

Variant names:

• chr2-95908690-A-T
• rs183934154
• NM_001393982.1:c.2865T>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001393982.1(ANKRD36C):​c.2865T>A​(p.Ser955Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,553,520 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00067 (3 hom., cov: 29)
  • Exomes 𝑓: 0.00046 (6 hom.)
• Consequence: ANKRD36C NM_001393982.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196
• Publications: 2 publications found

Genes affected

ANKRD36C (HGNC:32946): (ankyrin repeat domain 36C)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 2-95908690-A-T is Benign according to our data. Variant chr2-95908690-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.196 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393982.1. 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
	ANKRD36C	NM_001393982.1	MANE Select	c.2865T>A	p.Ser955Ser	synonymous	Exon 47 of 88	NP_001380911.1	A0A8J8YUB5
	ANKRD36C	NM_001310154.3		c.2940T>A	p.Ser980Ser	synonymous	Exon 48 of 89	NP_001297083.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36C	ENST00000295246.7	TSL:5 MANE Select	c.2865T>A	p.Ser955Ser	synonymous	Exon 47 of 88	ENSP00000295246.7	A0A8J8YUB5
	ANKRD36C	ENST00000456556.5	TSL:5	c.2653+3554T>A		intron	N/A	ENSP00000403302.1	Q5JPF3-1
	ANKRD36C	ENST00000534304.5	TSL:5	n.*981+3554T>A		intron	N/A	ENSP00000433685.1	H0YDI7

Frequencies

GnomAD3 genomes AF: 0.000669 AC: 101 AN: 150940 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.000315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000653

Gnomad OTH AF: 0.000965

GnomAD2 exomes AF: 0.000477 AC: 79 AN: 165748 AF XY: 0.000479

Gnomad AFR exome AF: 0.000116

Gnomad AMR exome AF: 0.000196

Gnomad ASJ exome AF: 0.000347

Gnomad EAS exome AF: 0.000171

Gnomad FIN exome AF: 0.00128

Gnomad NFE exome AF: 0.000542

Gnomad OTH exome AF: 0.000219

GnomAD4 exome AF: 0.000458 AC: 642 AN: 1402464 Hom.: 6 Cov.: 32 AF XY: 0.000483 AC XY: 335 AN XY: 693180

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000220 AC: 7 AN: 31792

American (AMR) AF: 0.000591 AC: 22 AN: 37254

Ashkenazi Jewish (ASJ) AF: 0.000720 AC: 18 AN: 25002

East Asian (EAS) AF: 0.000108 AC: 4 AN: 36890

South Asian (SAS) AF: 0.000300 AC: 24 AN: 79912

European-Finnish (FIN) AF: 0.00168 AC: 84 AN: 49904

Middle Eastern (MID) AF: 0.000250 AC: 1 AN: 4002

European-Non Finnish (NFE) AF: 0.000423 AC: 457 AN: 1079928

Other (OTH) AF: 0.000433 AC: 25 AN: 57780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000669 AC: 101 AN: 151056 Hom.: 3 Cov.: 29 AF XY: 0.000746 AC XY: 55 AN XY: 73752

African (AFR) AF: 0.000314 AC: 13 AN: 41348

American (AMR) AF: 0.00119 AC: 18 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5072

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4762

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000653 AC: 44 AN: 67386

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000408 Hom.: 20

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.27
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs183934154; hg19: chr2-96574438; COSMIC: COSV54760180; COSMIC: COSV54760180;