X-136227302-G-A

Variant names:

• chrX-136227302-G-A
• rs1046459058
• NM_024597.4:c.2016C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024597.4(MAP7D3):​c.2016C>T​(p.Asp672Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 (0 hom., 0 hem., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: MAP7D3 NM_024597.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 0 publications found

Genes affected

MAP7D3 (HGNC:25742): (MAP7 domain containing 3) The protein encoded by this gene belongs to the MAP7 (microtubule-associated protein 7) family. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Mar 2010]

MAP7D3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.429 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024597.4. 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
	MAP7D3	NM_024597.4	MANE Select	c.2016C>T	p.Asp672Asp	synonymous	Exon 12 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.1962C>T	p.Asp654Asp	synonymous	Exon 12 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.1911C>T	p.Asp637Asp	synonymous	Exon 11 of 18	NP_001166988.1	Q8IWC1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7D3	ENST00000316077.14	TSL:1 MANE Select	c.2016C>T	p.Asp672Asp	synonymous	Exon 12 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.1911C>T	p.Asp637Asp	synonymous	Exon 11 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.1893C>T	p.Asp631Asp	synonymous	Exon 12 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 108164 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181314 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000225

GnomAD4 exome Cov.: 29

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 108164 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 30500

African (AFR) AF: 0.00 AC: 0 AN: 29707

American (AMR) AF: 0.00 AC: 0 AN: 9940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2612

East Asian (EAS) AF: 0.00 AC: 0 AN: 3405

South Asian (SAS) AF: 0.00 AC: 0 AN: 2414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52407

Other (OTH) AF: 0.00 AC: 0 AN: 1457

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.51
DANN	Benign	0.37
PhyloP100		-0.43

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: rs1046459058; hg19: chrX-135309461;