rs6901

Variant names:

• chr10-3138035-T-A
• rs6901
• NM_014889.4:c.3110A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-3138035-T-A
• chr10-3138035-T-C
• chr10-3138035-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014889.4(PITRM1):​c.3110A>T​(p.Gln1037Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. Q1037R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITRM1 NM_014889.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939

Genes affected

PITRM1 (HGNC:17663): (pitrilysin metallopeptidase 1) The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]

ENSG00000278419 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09636733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4	c.3110A>T	p.Gln1037Leu	missense_variant	Exon 27 of 27	ENST00000224949.9	NP_055704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9	c.3110A>T	p.Gln1037Leu	missense_variant	Exon 27 of 27	1	NM_014889.4	ENSP00000224949.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.92e-7 AC: 1 AN: 1444304 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 717774

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T;.;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.096	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.13	N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Vest4		0.14
MutPred		0.43		.;Gain of stability (P = 0.0061);.;.;
MVP		0.12
MPC		0.050
ClinPred		0.69	D
GERP RS		0.73
Varity_R		0.11
gMVP		0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs6901; hg19: chr10-3180227;