NM_024597.4:c.1868G>T

Variant names:

• chrX-136228641-C-A
• rs756258024
• NM_024597.4:c.1868G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024597.4(MAP7D3):​c.1868G>T​(p.Arg623Leu) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R623Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAP7D3 NM_024597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.170
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22172812).

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.1868G>T	p.Arg623Leu	missense	Exon 11 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.1814G>T	p.Arg605Leu	missense	Exon 11 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.1763G>T	p.Arg588Leu	missense	Exon 10 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.1868G>T	p.Arg623Leu	missense	Exon 11 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.1763G>T	p.Arg588Leu	missense	Exon 10 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.1745G>T	p.Arg582Leu	missense	Exon 11 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.17
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.083
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.020	D
Polyphen		0.95	P
Vest4		0.24
MutPred		0.52		Loss of MoRF binding (P = 0.0794)
MVP		0.23
MPC		0.28
ClinPred		0.97	D
GERP RS		-2.3
Varity_R		0.24
gMVP		0.017
Mutation Taster		=87/13	polymorphism

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: rs756258024; hg19: chrX-135310800; COSMIC: COSV100286717; COSMIC: COSV100286717;