6-136359992-C-T

Variant names:

• chr6-136359992-C-T
• rs147645484
• NM_003980.6:c.1843G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003980.6(MAP7):​c.1843G>A​(p.Ala615Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,504 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (21 hom.)
• Consequence: MAP7 NM_003980.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179
• Publications: 3 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004345447).
• BP6: Variant 6-136359992-C-T is Benign according to our data. Variant chr6-136359992-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

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.1843G>A	p.Ala615Thr	missense	Exon 14 of 18	NP_003971.1	Q14244-1
	MAP7	NM_001198609.2		c.1933G>A	p.Ala645Thr	missense	Exon 14 of 18	NP_001185538.1	A0A087WZ40
	MAP7	NM_001388328.1		c.1933G>A	p.Ala645Thr	missense	Exon 15 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.1843G>A	p.Ala615Thr	missense	Exon 14 of 18	ENSP00000346581.2	Q14244-1
	MAP7	ENST00000617204.4	TSL:2	c.1933G>A	p.Ala645Thr	missense	Exon 14 of 18	ENSP00000482335.1	A0A087WZ40
	MAP7	ENST00000877105.1		c.1930G>A	p.Ala644Thr	missense	Exon 15 of 19	ENSP00000547164.1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00255 AC: 641 AN: 250918 AF XY: 0.00293

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000900

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00624

Gnomad NFE exome AF: 0.00168

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00207 AC: 3026 AN: 1461206 Hom.: 21 Cov.: 31 AF XY: 0.00232 AC XY: 1683 AN XY: 726852

African (AFR) AF: 0.000239 AC: 8 AN: 33434

American (AMR) AF: 0.000762 AC: 34 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.00855 AC: 735 AN: 85984

European-Finnish (FIN) AF: 0.00642 AC: 343 AN: 53410

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5762

European-Non Finnish (NFE) AF: 0.00162 AC: 1797 AN: 1111828

Other (OTH) AF: 0.00164 AC: 99 AN: 60360

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74478

African (AFR) AF: 0.000192 AC: 8 AN: 41566

American (AMR) AF: 0.000915 AC: 14 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00891 AC: 43 AN: 4826

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68014

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.000880

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00271 AC: 329

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00175

EpiControl AF: 0.00160

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.18
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.044
Sift	Benign	0.32	T
Sift4G	Benign	0.22	T
Polyphen		0.65	P
Vest4		0.23
MVP		0.30
MPC		0.15
ClinPred		0.028	T
GERP RS		4.0
Varity_R		0.036
gMVP		0.076
Mutation Taster		=97/3	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: rs147645484; hg19: chr6-136681130; COSMIC: COSV63423358; COSMIC: COSV63423358;