Variant 5-135343265-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_138610.3(MACROH2A1):c.948C>T(p.Ser316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MACROH2A1
NM_138610.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.865

Variant links:

Genes affected

MACROH2A1 (HGNC:4740): (macroH2A.1 histone) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-independent histone that is a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and participates in stable X chromosome inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]

MACROH2A1 links:

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

PITX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 5-135343265-G-A is Benign according to our data. Variant chr5-135343265-G-A is described in ClinVar as [Benign]. Clinvar id is 716117.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.865 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROH2A1	NM_138610.3 linkuse as main transcript	c.948C>T	p.Ser316=	synonymous_variant	8/9	ENST00000511689.6
PITX1-AS1	NR_161235.1 linkuse as main transcript	n.1065G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROH2A1	ENST00000511689.6 linkuse as main transcript	c.948C>T	p.Ser316=	synonymous_variant	8/9	1	NM_138610.3	A1	O75367-1
PITX1-AS1	ENST00000624272.3 linkuse as main transcript	n.1059G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000338

AC:

AN:

251358

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00498

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461750

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00472

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152236

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00462

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000573

Hom.:

Bravo

AF:

0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.35

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over