rs200510790

Variant names:

• chrX-136228631-C-A
• rs200510790
• NM_024597.4:c.1878G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024597.4(MAP7D3):​c.1878G>T​(p.Met626Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,204,746 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., 22 hem., cov: 23)
  • Exomes 𝑓: 0.000073 (0 hom. 14 hem.)
• Consequence: MAP7D3 NM_024597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061146617).
• BS2: High Hemizygotes in GnomAd4 at 22 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.1878G>T	p.Met626Ile	missense	Exon 11 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.1824G>T	p.Met608Ile	missense	Exon 11 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.1773G>T	p.Met591Ile	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.1878G>T	p.Met626Ile	missense	Exon 11 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.1773G>T	p.Met591Ile	missense	Exon 10 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.1755G>T	p.Met585Ile	missense	Exon 11 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 84 AN: 112192 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00262

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000190

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: 0.000666

GnomAD2 exomes AF: 0.000210 AC: 36 AN: 171416 AF XY: 0.000120

Gnomad AFR exome AF: 0.00284

Gnomad AMR exome AF: 0.0000799

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: 0.00

GnomAD4 exome AF: 0.0000732 AC: 80 AN: 1092554 Hom.: 0 Cov.: 29 AF XY: 0.0000390 AC XY: 14 AN XY: 358636

African (AFR) AF: 0.00244 AC: 64 AN: 26184

American (AMR) AF: 0.000117 AC: 4 AN: 34322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19282

East Asian (EAS) AF: 0.00 AC: 0 AN: 29687

South Asian (SAS) AF: 0.00 AC: 0 AN: 53022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40445

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4105

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839608

Other (OTH) AF: 0.000218 AC: 10 AN: 45899

GnomAD4 genome AF: 0.000749 AC: 84 AN: 112192 Hom.: 0 Cov.: 23 AF XY: 0.000640 AC XY: 22 AN XY: 34352

African (AFR) AF: 0.00262 AC: 81 AN: 30875

American (AMR) AF: 0.000190 AC: 2 AN: 10554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3595

South Asian (SAS) AF: 0.00 AC: 0 AN: 2721

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6097

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53279

Other (OTH) AF: 0.000666 AC: 1 AN: 1501

Alfa AF: 0.000321 Hom.: 14

Bravo AF: 0.000903

ESP6500AA AF: 0.00320 AC: 10

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000232 AC: 28

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	Uncertain	0.49
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.43
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.013
Sift	Benign	0.47	T
Sift4G	Benign	0.23	T
Polyphen		0.12	B
Vest4		0.17
MutPred		0.28		Gain of MoRF binding (P = 0.1385)
MVP		0.40
MPC		0.12
ClinPred		0.0051	T
GERP RS		0.020
Varity_R		0.11
gMVP		0.019
Mutation Taster		=99/1	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: rs200510790; hg19: chrX-135310790; COSMIC: COSV100286870; COSMIC: COSV100286870;