NM_017747.3:c.1590T>C

Variant names:

• chr5-140459273-T-C
• rs372120011
• NM_017747.3:c.1590T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_017747.3(ANKHD1):​c.1590T>C​(p.Asp530Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,603,396 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000096 (4 hom.)
• Consequence: ANKHD1 NM_017747.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.156
• Publications: 0 publications found

Genes affected

ANKHD1 (HGNC:24714): (ankyrin repeat and KH domain containing 1) This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]

ANKHD1-EIF4EBP3 (HGNC:33530): (ANKHD1-EIF4EBP3 readthrough) The ANKHD1-EIF4EBP3 mRNA is an infrequent but naturally occurring readthrough transcript of the neighboring ANKHD1 and EIF4EBP3 genes. This readthrough transcript encodes a protein composed mostly of the multiple ankyrin repeats, single KH-domain protein, with its C-terminus encoded in a different reading frame from the shared portion of the EIF4EBP3 gene. The significance of this readthrough mRNA and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.118).
• BP6: Variant 5-140459273-T-C is Benign according to our data. Variant chr5-140459273-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2655738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.156 with no splicing effect.
• BS2: High AC in GnomAd4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017747.3. 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
	ANKHD1	NM_017747.3	MANE Select	c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 34	NP_060217.1	Q8IWZ3-1
	ANKHD1-EIF4EBP3	NM_020690.6		c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 36	NP_065741.3
	ANKHD1	NM_024668.4		c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 11	NP_078944.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKHD1	ENST00000360839.7	TSL:1 MANE Select	c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 34	ENSP00000354085.2	Q8IWZ3-1
	ANKHD1-EIF4EBP3	ENST00000532219.5	TSL:2	c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 36	ENSP00000432016.1
	ANKHD1	ENST00000394723.7	TSL:1	c.1590T>C	p.Asp530Asp	synonymous	Exon 9 of 11	ENSP00000378212.3	Q8IWZ3-2

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 151782 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000412

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000962

GnomAD2 exomes AF: 0.000153 AC: 38 AN: 248392 AF XY: 0.0000893

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00126

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000989

GnomAD4 exome AF: 0.0000958 AC: 139 AN: 1451614 Hom.: 4 Cov.: 30 AF XY: 0.0000734 AC XY: 53 AN XY: 722440

African (AFR) AF: 0.0000599 AC: 2 AN: 33384

American (AMR) AF: 0.0000898 AC: 4 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25816

East Asian (EAS) AF: 0.000657 AC: 26 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 85252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000543 AC: 6 AN: 1104654

Other (OTH) AF: 0.00169 AC: 101 AN: 59732

GnomAD4 genome AF: 0.000204 AC: 31 AN: 151782 Hom.: 0 Cov.: 31 AF XY: 0.000135 AC XY: 10 AN XY: 74110

African (AFR) AF: 0.000412 AC: 17 AN: 41306

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67944

Other (OTH) AF: 0.000962 AC: 2 AN: 2078

Alfa AF: 0.000305 Hom.: 0

Bravo AF: 0.000314

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.51
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.16
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

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: rs372120011; hg19: chr5-139838858;