chr17-6451782-GT-G

Variant names:

• chr17-6451782-GT-G
• rs61555153
• NM_031220.4:c.*3555delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031220.4(PITPNM3):​c.*3555delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (60964 hom., cov: 0)
  • Exomes 𝑓: 0.83 (8 hom.)
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.604
• Publications: 2 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]

PITPNM3 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 5

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-6451782-GT-G is Benign according to our data. Variant chr17-6451782-GT-G is described in ClinVar as Benign. ClinVar VariationId is 324659.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 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.*3555delA		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3555delA		3_prime_UTR	Exon 19 of 19	NP_001159438.1	Q9BZ71-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	ENST00000262483.13	TSL:1 MANE Select	c.*3555delA		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3555delA		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes AF: 0.895 AC: 135661 AN: 151506 Hom.: 60917 Cov.: 0

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.890

GnomAD4 exome AF: 0.833 AC: 20 AN: 24 Hom.: 8 Cov.: 0 AF XY: 0.850 AC XY: 17 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.850 AC: 17 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.895 AC: 135765 AN: 151622 Hom.: 60964 Cov.: 0 AF XY: 0.895 AC XY: 66264 AN XY: 74044

African (AFR) AF: 0.948 AC: 39162 AN: 41290

American (AMR) AF: 0.877 AC: 13363 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3039 AN: 3468

East Asian (EAS) AF: 0.853 AC: 4360 AN: 5114

South Asian (SAS) AF: 0.856 AC: 4113 AN: 4804

European-Finnish (FIN) AF: 0.859 AC: 9007 AN: 10482

Middle Eastern (MID) AF: 0.911 AC: 266 AN: 292

European-Non Finnish (NFE) AF: 0.880 AC: 59761 AN: 67918

Other (OTH) AF: 0.890 AC: 1878 AN: 2110

Alfa AF: 0.890 Hom.: 6462

Bravo AF: 0.893

Asia WGS AF: 0.848 AC: 2949 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-Rod Dystrophy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
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: rs61555153; hg19: chr17-6355102; COSMIC: COSV51470162; COSMIC: COSV51470162;