1-36171169-C-T

Variant names:

• chr1-36171169-C-T
• rs138447994
• NM_001388490.1:c.245C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001388490.1(MAP7D1):​c.245C>T​(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MAP7D1 NM_001388490.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.07
• Publications: 3 publications found

Genes affected

MAP7D1 (HGNC:25514): (MAP7 domain containing 1) Predicted to be involved in microtubule cytoskeleton organization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040492535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388490.1. 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
	MAP7D1	NM_001388490.1	MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 2 of 17	NP_001375419.1	D3DPS3
	MAP7D1	NM_018067.5		c.245C>T	p.Pro82Leu	missense	Exon 2 of 17	NP_060537.3
	MAP7D1	NM_001286366.2		c.245C>T	p.Pro82Leu	missense	Exon 2 of 18	NP_001273295.1	Q3KQU3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7D1	ENST00000474796.2	TSL:2 MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 2 of 17	ENSP00000507044.1	D3DPS3
	MAP7D1	ENST00000373151.6	TSL:1	c.245C>T	p.Pro82Leu	missense	Exon 2 of 17	ENSP00000362244.2	Q3KQU3-1
	MAP7D1	ENST00000316156.8	TSL:1	c.245C>T	p.Pro82Leu	missense	Exon 2 of 16	ENSP00000320228.4	Q3KQU3-2

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000640 AC: 16 AN: 250050 AF XY: 0.0000813

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000135 AC: 198 AN: 1461686 Hom.: 0 Cov.: 33 AF XY: 0.000149 AC XY: 108 AN XY: 727138

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000149 AC: 166 AN: 1111928

Other (OTH) AF: 0.000116 AC: 7 AN: 60380

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152168 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74330

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.061
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.17
DANN	Benign	0.77
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		-3.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.011
Sift	Uncertain	0.011	D
Sift4G	Benign	0.078	T
Polyphen		0.0010	B
Vest4		0.073
MVP		0.043
MPC		0.12
ClinPred		0.028	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.13
Mutation Taster		=99/1	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: rs138447994; hg19: chr1-36636770; COSMIC: COSV60216319; COSMIC: COSV60216319;