X-136228641-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D3	NM_024597.4	c.1868G>T	p.Arg623Leu	missense_variant	Exon 11 of 19	ENST00000316077.14	NP_078873.2
MAP7D3	NM_001173516.1	c.1814G>T	p.Arg605Leu	missense_variant	Exon 11 of 19		NP_001166987.1
MAP7D3	NM_001173517.2	c.1763G>T	p.Arg588Leu	missense_variant	Exon 10 of 18		NP_001166988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP7D3	ENST00000316077.14	c.1868G>T	p.Arg623Leu	missense_variant	Exon 11 of 19	1	NM_024597.4	ENSP00000318086.9

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1868G>T (p.R623L) alteration is located in exon 11 (coding exon 11) of the MAP7D3 gene. This alteration results from a G to T substitution at nucleotide position 1868, causing the arginine (R) at amino acid position 623 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.62	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.083
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.020	D;D;D;.
Polyphen		0.95	P;D;.;.
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

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