chrX-136219623-C-T

Variant names:

• chrX-136219623-C-T
• rs370445924
• NM_024597.4:c.2535G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_024597.4(MAP7D3):​c.2535G>A​(p.Ala845Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,206,522 control chromosomes in the GnomAD database, including 1 homozygotes. There are 66 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00017 (1 hom. 61 hem.)
• Consequence: MAP7D3 NM_024597.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.29
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-136219623-C-T is Benign according to our data. Variant chrX-136219623-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3045196.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 5 XL gene

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.2535G>A	p.Ala845Ala	synonymous	Exon 17 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.2481G>A	p.Ala827Ala	synonymous	Exon 17 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.2430G>A	p.Ala810Ala	synonymous	Exon 16 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.2535G>A	p.Ala845Ala	synonymous	Exon 17 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.2430G>A	p.Ala810Ala	synonymous	Exon 16 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000945657.1		c.2565G>A	p.Ala855Ala	synonymous	Exon 18 of 20	ENSP00000615716.1

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 18 AN: 111991 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000650

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000368

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000716 AC: 13 AN: 181464 AF XY: 0.0000297

Gnomad AFR exome AF: 0.000161

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000738

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000984

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000173 AC: 189 AN: 1094479 Hom.: 1 Cov.: 29 AF XY: 0.000169 AC XY: 61 AN XY: 360075

African (AFR) AF: 0.0000758 AC: 2 AN: 26369

American (AMR) AF: 0.0000284 AC: 1 AN: 35183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19330

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30196

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40509

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.000203 AC: 170 AN: 838703

Other (OTH) AF: 0.000304 AC: 14 AN: 45982

GnomAD4 genome AF: 0.000161 AC: 18 AN: 112043 Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 5 AN XY: 34247

African (AFR) AF: 0.0000648 AC: 2 AN: 30859

American (AMR) AF: 0.00 AC: 0 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00 AC: 0 AN: 3578

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000282 AC: 15 AN: 53165

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000140

EpiCase AF: 0.000109

EpiControl AF: 0.000358

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MAP7D3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.17
DANN	Benign	0.38
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs370445924; hg19: chrX-135301782; COSMIC: COSV60171063; COSMIC: COSV60171063;