6-136361111-C-G

Variant names:

• chr6-136361111-C-G
• rs896174811
• NM_003980.6:c.1595G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003980.6(MAP7):​c.1595G>C​(p.Arg532Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R532L) has been classified as Uncertain significance.

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

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]

ENSG00000293092 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003980.6. 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
	MAP7	NM_003980.6	MANE Select	c.1595G>C	p.Arg532Pro	missense	Exon 12 of 18	NP_003971.1	Q14244-1
	MAP7	NM_001198609.2		c.1685G>C	p.Arg562Pro	missense	Exon 12 of 18	NP_001185538.1	A0A087WZ40
	MAP7	NM_001388328.1		c.1685G>C	p.Arg562Pro	missense	Exon 13 of 19	NP_001375257.1	A0A087WZ40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7	ENST00000354570.8	TSL:1 MANE Select	c.1595G>C	p.Arg532Pro	missense	Exon 12 of 18	ENSP00000346581.2	Q14244-1
	MAP7	ENST00000617204.4	TSL:2	c.1685G>C	p.Arg562Pro	missense	Exon 12 of 18	ENSP00000482335.1	A0A087WZ40
	MAP7	ENST00000877105.1		c.1682G>C	p.Arg561Pro	missense	Exon 13 of 19	ENSP00000547164.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.0043
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.1
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.19
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.029	D
Polyphen		0.98	D
Vest4		0.53
MutPred		0.49		Gain of loop (P = 0.002)
MVP		0.51
MPC		0.22
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.80
gMVP		0.076
Mutation Taster		=86/14	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: rs896174811; hg19: chr6-136682249;