NM_024597.4:c.2330C>T

Variant names:

• chrX-136220921-G-A
• rs776578303
• NM_024597.4:c.2330C>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.2330C>T​(p.Pro777Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,207,272 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000016 (0 hom. 7 hem.)
• Consequence: MAP7D3 NM_024597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.433
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04236269).
• BS2: High Hemizygotes in GnomAdExome4 at 7 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.2330C>T	p.Pro777Leu	missense	Exon 16 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.2276C>T	p.Pro759Leu	missense	Exon 16 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.2225C>T	p.Pro742Leu	missense	Exon 15 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.2330C>T	p.Pro777Leu	missense	Exon 16 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.2225C>T	p.Pro742Leu	missense	Exon 15 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.2207C>T	p.Pro736Leu	missense	Exon 16 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111965 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000325

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: 0.0000385 AC: 7 AN: 181687 AF XY: 0.0000296

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: 0.000224

GnomAD4 exome AF: 0.0000164 AC: 18 AN: 1095307 Hom.: 0 Cov.: 29 AF XY: 0.0000194 AC XY: 7 AN XY: 360767

African (AFR) AF: 0.00 AC: 0 AN: 26355

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19367

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30193

South Asian (SAS) AF: 0.000185 AC: 10 AN: 54054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00000596 AC: 5 AN: 839470

Other (OTH) AF: 0.0000435 AC: 2 AN: 46007

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111965 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34161

African (AFR) AF: 0.0000325 AC: 1 AN: 30725

American (AMR) AF: 0.00 AC: 0 AN: 10557

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3592

South Asian (SAS) AF: 0.00 AC: 0 AN: 2640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

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

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000248 AC: 3

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	0.12
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.32
DEOGEN2	Benign	0.0083	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.43
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.045
Sift	Benign	0.099	T
Sift4G	Benign	0.66	T
Polyphen		0.79	P
Vest4		0.084
MutPred		0.30		Loss of disorder (P = 0.0384)
MVP		0.16
MPC		0.097
ClinPred		0.025	T
GERP RS		-3.3
Varity_R		0.031
gMVP		0.029
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: rs776578303; hg19: chrX-135303080;