17-6451645-T-C

Variant names:

• chr17-6451645-T-C
• rs3169862
• NM_031220.4:c.*3693A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031220.4(PITPNM3):​c.*3693A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,032 control chromosomes in the GnomAD database, including 23,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23548 hom., cov: 31)
  • Exomes 𝑓: 0.57 (24 hom.)
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.191
• Publications: 5 publications found

Genes affected

PITPNM3 (HGNC:21043): (PITPNM family member 3) This gene encodes a member of a family of membrane-associated phosphatidylinositol transfer domain-containing proteins. The calcium-binding protein has phosphatidylinositol (PI) transfer activity and interacts with the protein tyrosine kinase PTK2B (also known as PYK2). The protein is homologous to a Drosophila protein that is implicated in the visual transduction pathway in flies. Mutations in this gene result in autosomal dominant cone dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

PIMREG (HGNC:25483): (PICALM interacting mitotic regulator) Predicted to be involved in cell division. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-6451645-T-C is Benign according to our data. Variant chr17-6451645-T-C is described in ClinVar as Benign. ClinVar VariationId is 324657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031220.4. 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
	PITPNM3	NM_031220.4	MANE Select	c.*3693A>G		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3693A>G		3_prime_UTR	Exon 19 of 19	NP_001159438.1	Q9BZ71-3
	PIMREG	NM_019013.3	MANE Select	c.*1298T>C		downstream_gene	N/A	NP_061886.2	Q9BSJ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	ENST00000262483.13	TSL:1 MANE Select	c.*3693A>G		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3693A>G		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3
	PIMREG	ENST00000572447.6	TSL:1 MANE Select	c.*1298T>C		downstream_gene	N/A	ENSP00000459235.1	Q9BSJ6-2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83623 AN: 151796 Hom.: 23524 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.568 AC: 67 AN: 118 Hom.: 24 Cov.: 0 AF XY: 0.486 AC XY: 34 AN XY: 70

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 3 AN: 4

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.444 AC: 8 AN: 18

Middle Eastern (MID) AF: 0.850 AC: 17 AN: 20

European-Non Finnish (NFE) AF: 0.500 AC: 32 AN: 64

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.551 AC: 83693 AN: 151914 Hom.: 23548 Cov.: 31 AF XY: 0.544 AC XY: 40376 AN XY: 74256

African (AFR) AF: 0.582 AC: 24081 AN: 41400

American (AMR) AF: 0.590 AC: 9007 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1439 AN: 5154

South Asian (SAS) AF: 0.437 AC: 2101 AN: 4804

European-Finnish (FIN) AF: 0.453 AC: 4779 AN: 10558

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38291 AN: 67942

Other (OTH) AF: 0.583 AC: 1227 AN: 2106

Alfa AF: 0.557 Hom.: 45295

Bravo AF: 0.564

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs3169862; hg19: chr17-6354965;