X-136224853-T-G

Variant names:

• chrX-136224853-T-G
• rs774025753
• NM_024597.4:c.2167A>C

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.2167A>C​(p.Arg723Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,066,952 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: MAP7D3 NM_024597.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• 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=-0.83).
• BP7: Synonymous conserved (PhyloP=0.528 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.2167A>C	p.Arg723Arg	synonymous	Exon 14 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.2113A>C	p.Arg705Arg	synonymous	Exon 14 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.2062A>C	p.Arg688Arg	synonymous	Exon 13 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.2167A>C	p.Arg723Arg	synonymous	Exon 14 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.2062A>C	p.Arg688Arg	synonymous	Exon 13 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.2044A>C	p.Arg682Arg	synonymous	Exon 14 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1066952 Hom.: 0 Cov.: 23 AF XY: 0.00000296 AC XY: 1 AN XY: 337856

African (AFR) AF: 0.00 AC: 0 AN: 25917

American (AMR) AF: 0.00 AC: 0 AN: 35098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19181

East Asian (EAS) AF: 0.00 AC: 0 AN: 30035

South Asian (SAS) AF: 0.0000375 AC: 2 AN: 53288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4051

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 813936

Other (OTH) AF: 0.00 AC: 0 AN: 45056

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.53
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774025753; hg19: chrX-135307012;