Genetic Variant MAP7D3:p.Lys720Lys (chrX-136224860-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_024597.4(MAP7D3):c.2160G>A(p.Lys720Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000277 in 1,167,847 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 86 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 37 hem., cov: 24)

Exomes 𝑓: 0.00018 ( 0 hom. 49 hem. )

Consequence

MAP7D3
NM_024597.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.753

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant X-136224860-C-T is Benign according to our data. Variant chrX-136224860-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050155.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.753 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7D3	NM_024597.4 link	c.2160G>A	p.Lys720Lys	synonymous_variant	Exon 14 of 19	ENST00000316077.14	NP_078873.2	Q8IWC1-1
MAP7D3	NM_001173516.1 link	c.2106G>A	p.Lys702Lys	synonymous_variant	Exon 14 of 19		NP_001166987.1	Q8IWC1-4
MAP7D3	NM_001173517.2 link	c.2055G>A	p.Lys685Lys	synonymous_variant	Exon 13 of 18		NP_001166988.1	Q8IWC1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP7D3	ENST00000316077.14 link	c.2160G>A	p.Lys720Lys	synonymous_variant	Exon 14 of 19	1	NM_024597.4	ENSP00000318086.9		Q8IWC1-1

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

133

AN:

112340

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

34518

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000753

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:

0.00266

GnomAD3 exomes

AF:

0.000388

AC:

AN:

177664

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

63792

show subpopulations

Gnomad AFR exome

AF:

0.00507

Gnomad AMR exome

AF:

0.000224

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000178

AC:

188

AN:

1055454

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

327936

show subpopulations

Gnomad4 AFR exome

AF:

0.00556

Gnomad4 AMR exome

AF:

0.000200

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000124

Gnomad4 OTH exome

AF:

0.000829

GnomAD4 genome

AF:

0.00120

AC:

135

AN:

112393

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

34581

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.000752

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00262

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAP7D3-related disorder

Benign:1

Jul 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.4

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over