chr22-50249919-A-G

Variant names:

• chr22-50249919-A-G
• rs1555048
• NM_032019.6:c.435T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032019.6(HDAC10):​c.435T>C​(p.Cys145Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 1,612,280 control chromosomes in the GnomAD database, including 437,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (48709 hom., cov: 32)
  • Exomes 𝑓: 0.73 (388875 hom.)
• Consequence: HDAC10 NM_032019.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 45 publications found

Genes affected

HDAC10 (HGNC:18128): (histone deacetylase 10) The protein encoded by this gene belongs to the histone deacetylase family, members of which deacetylate lysine residues on the N-terminal part of the core histones. Histone deacetylation modulates chromatin structure, and plays an important role in transcriptional regulation, cell cycle progression, and developmental events. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MAPK12 (HGNC:6874): (mitogen-activated protein kinase 12) Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.271 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC10	NM_032019.6	c.435T>C	p.Cys145Cys	synonymous_variant	Exon 5 of 20	ENST00000216271.10	NP_114408.3
HDAC10	NM_001159286.2	c.435T>C	p.Cys145Cys	synonymous_variant	Exon 5 of 19		NP_001152758.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC10	ENST00000216271.10	c.435T>C	p.Cys145Cys	synonymous_variant	Exon 5 of 20	1	NM_032019.6	ENSP00000216271.5

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120421 AN: 151942 Hom.: 48651 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.771

GnomAD2 exomes AF: 0.782 AC: 195080 AN: 249318 AF XY: 0.779

Gnomad AFR exome AF: 0.950

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.855

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.726 AC: 1060620 AN: 1460220 Hom.: 388875 Cov.: 52 AF XY: 0.729 AC XY: 529773 AN XY: 726428

African (AFR) AF: 0.949 AC: 31779 AN: 33472

American (AMR) AF: 0.857 AC: 38280 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 19029 AN: 26114

East Asian (EAS) AF: 0.845 AC: 33540 AN: 39684

South Asian (SAS) AF: 0.892 AC: 76956 AN: 86250

European-Finnish (FIN) AF: 0.731 AC: 38271 AN: 52334

Middle Eastern (MID) AF: 0.726 AC: 4186 AN: 5766

European-Non Finnish (NFE) AF: 0.696 AC: 773467 AN: 1111564

Other (OTH) AF: 0.748 AC: 45112 AN: 60344

GnomAD4 genome AF: 0.793 AC: 120536 AN: 152060 Hom.: 48709 Cov.: 32 AF XY: 0.798 AC XY: 59280 AN XY: 74306

African (AFR) AF: 0.944 AC: 39186 AN: 41506

American (AMR) AF: 0.813 AC: 12428 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2571 AN: 3470

East Asian (EAS) AF: 0.847 AC: 4357 AN: 5144

South Asian (SAS) AF: 0.901 AC: 4347 AN: 4826

European-Finnish (FIN) AF: 0.724 AC: 7643 AN: 10560

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47593 AN: 67960

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.742 Hom.: 113852

Bravo AF: 0.804

Asia WGS AF: 0.860 AC: 2993 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.50
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs1555048; hg19: chr22-50688348; COSMIC: COSV108029439; COSMIC: COSV108029439;