6-136361111-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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. R532L) 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
• 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 1 ACMG points.

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

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>A	p.Arg532His	missense	Exon 12 of 18	NP_003971.1	Q14244-1
	MAP7	NM_001198609.2		c.1685G>A	p.Arg562His	missense	Exon 12 of 18	NP_001185538.1	A0A087WZ40
	MAP7	NM_001388328.1		c.1685G>A	p.Arg562His	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>A	p.Arg532His	missense	Exon 12 of 18	ENSP00000346581.2	Q14244-1
	MAP7	ENST00000617204.4	TSL:2	c.1685G>A	p.Arg562His	missense	Exon 12 of 18	ENSP00000482335.1	A0A087WZ40
	MAP7	ENST00000877105.1		c.1682G>A	p.Arg561His	missense	Exon 13 of 19	ENSP00000547164.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111836

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.026
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	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
Mutation Taster		=95/5	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;