NM_024597.4:c.2081A>G

Variant names:

• chrX-136225967-T-C
• rs377561911
• NM_024597.4:c.2081A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_024597.4(MAP7D3):​c.2081A>G​(p.Lys694Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,204,925 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.00017 (0 hom. 41 hem.)
• Consequence: MAP7D3 NM_024597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10822013).
• BS2: High Hemizygotes in GnomAdExome4 at 41 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.2081A>G	p.Lys694Arg	missense	Exon 13 of 19	NP_078873.2
	MAP7D3	NM_001173516.1		c.2027A>G	p.Lys676Arg	missense	Exon 13 of 19	NP_001166987.1	Q8IWC1-4
	MAP7D3	NM_001173517.2		c.1976A>G	p.Lys659Arg	missense	Exon 12 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.2081A>G	p.Lys694Arg	missense	Exon 13 of 19	ENSP00000318086.9	Q8IWC1-1
	MAP7D3	ENST00000370661.5	TSL:1	c.1976A>G	p.Lys659Arg	missense	Exon 12 of 18	ENSP00000359695.1	Q8IWC1-3
	MAP7D3	ENST00000370660.3	TSL:1	c.1958A>G	p.Lys653Arg	missense	Exon 13 of 17	ENSP00000359694.3	A0A0A0MRP0

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111959 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000286 AC: 5 AN: 175014 AF XY: 0.0000326

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: 0.0000626

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000166 AC: 181 AN: 1092966 Hom.: 0 Cov.: 27 AF XY: 0.000114 AC XY: 41 AN XY: 358598

African (AFR) AF: 0.00 AC: 0 AN: 26217

American (AMR) AF: 0.00 AC: 0 AN: 34658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19305

East Asian (EAS) AF: 0.00 AC: 0 AN: 30081

South Asian (SAS) AF: 0.00 AC: 0 AN: 52654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40471

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4120

European-Non Finnish (NFE) AF: 0.000212 AC: 178 AN: 839519

Other (OTH) AF: 0.0000653 AC: 3 AN: 45941

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111959 Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1 AN XY: 34105

African (AFR) AF: 0.00 AC: 0 AN: 30790

American (AMR) AF: 0.00 AC: 0 AN: 10475

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3613

South Asian (SAS) AF: 0.00 AC: 0 AN: 2656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6095

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

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53248

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000189

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000156 AC: 1

ExAC AF: 0.0000414 AC: 5

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	0.15
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N
PhyloP100		1.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.062
Sift	Benign	0.33	T
Sift4G	Benign	0.94	T
Polyphen		0.99	D
Vest4		0.19
MVP		0.38
MPC		0.37
ClinPred		0.13	T
GERP RS		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.092
gMVP		0.0096
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs377561911; hg19: chrX-135308126;