6-136361111-C-T

Variant names:

• chr6-136361111-C-T
• NM_003980.6:c.1595G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003980.6(MAP7):​c.1595G>A​(p.Arg532His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R532C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAP7 NM_003980.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

MAP7 (HGNC:6869): (microtubule associated protein 7) The product of this gene is a microtubule-associated protein that is predominantly expressed in cells of epithelial origin. Microtubule-associated proteins are thought to be involved in microtubule dynamics, which is essential for cell polarization and differentiation. This protein has been shown to be able to stabilize microtubules, and may serve to modulate microtubule functions. Studies of the related mouse protein also suggested an essential role in microtubule function required for spermatogenesis. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28762257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP7	NM_003980.6	c.1595G>A	p.Arg532His	missense_variant	Exon 12 of 18	ENST00000354570.8	NP_003971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP7	ENST00000354570.8	c.1595G>A	p.Arg532His	missense_variant	Exon 12 of 18	1	NM_003980.6	ENSP00000346581.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453272 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 723358

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.14	T;.;.;.;T;.;.;.;.
Eigen	Benign	0.026
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.86	D;T;T;T;T;D;D;D;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.4	.;.;.;.;M;.;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	.;N;.;.;D;N;N;N;.
REVEL	Benign	0.16
Sift	Uncertain	0.014	.;D;.;.;D;D;D;D;.
Sift4G	Uncertain	0.029	D;D;D;D;D;D;D;D;D
Polyphen		0.99, 0.99	.;.;.;D;D;.;.;.;.
Vest4		0.39
MutPred		0.55		.;.;.;.;Gain of loop (P = 0.0502);.;.;.;.;
MVP		0.58
MPC		0.19
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.026

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: chr6-136682249;