6-136362471-C-T

Variant names:

• chr6-136362471-C-T
• rs1793106343
• NM_003980.6:c.1505G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003980.6(MAP7):​c.1505G>A​(p.Arg502Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MAP7 NM_003980.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.501
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027436405).
• BP6: Variant 6-136362471-C-T is Benign according to our data. Variant chr6-136362471-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3870366.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1505G>A	p.Arg502Lys	missense	Exon 11 of 18	NP_003971.1	Q14244-1
	MAP7	NM_001198609.2		c.1595G>A	p.Arg532Lys	missense	Exon 11 of 18	NP_001185538.1	A0A087WZ40
	MAP7	NM_001388328.1		c.1595G>A	p.Arg532Lys	missense	Exon 12 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.1505G>A	p.Arg502Lys	missense	Exon 11 of 18	ENSP00000346581.2	Q14244-1
	MAP7	ENST00000617204.4	TSL:2	c.1595G>A	p.Arg532Lys	missense	Exon 11 of 18	ENSP00000482335.1	A0A087WZ40
	MAP7	ENST00000877105.1		c.1592G>A	p.Arg531Lys	missense	Exon 12 of 19	ENSP00000547164.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000478

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.55
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.89	L
PhyloP100		0.50
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.030
Sift	Benign	0.48	T
Sift4G	Benign	0.38	T
Polyphen		0.0090	B
Vest4		0.19
MutPred		0.47		Gain of ubiquitination at R502 (P = 0.0121)
MVP		0.23
MPC		0.15
ClinPred		0.029	T
GERP RS		0.49
Varity_R		0.057
gMVP		0.10
Mutation Taster		=94/6	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: rs1793106343; hg19: chr6-136683609;