17-6451777-C-T

Variant names:

• chr17-6451777-C-T
• rs57360986
• NM_031220.4:c.*3561G>A

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.*3561G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 45,966 control chromosomes in the GnomAD database, including 615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (615 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PITPNM3 NM_031220.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.506
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-6451777-C-T is Benign according to our data. Variant chr17-6451777-C-T is described in ClinVar as Benign. ClinVar VariationId is 324658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.418 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.*3561G>A		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3561G>A		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.*3561G>A		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3561G>A		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 9567 AN: 45904 Hom.: 612 Cov.: 23

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.206

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 16

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.209 AC: 9588 AN: 45966 Hom.: 615 Cov.: 23 AF XY: 0.203 AC XY: 4460 AN XY: 21996

African (AFR) AF: 0.427 AC: 6753 AN: 15830

American (AMR) AF: 0.139 AC: 608 AN: 4380

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 107 AN: 984

East Asian (EAS) AF: 0.00 AC: 0 AN: 1320

South Asian (SAS) AF: 0.0477 AC: 62 AN: 1300

European-Finnish (FIN) AF: 0.0194 AC: 54 AN: 2788

Middle Eastern (MID) AF: 0.100 AC: 6 AN: 60

European-Non Finnish (NFE) AF: 0.0993 AC: 1831 AN: 18432

Other (OTH) AF: 0.203 AC: 128 AN: 630

Alfa AF: 0.105 Hom.: 222

Bravo AF: 0.0713

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	-0.81
CADD	Benign	9.3
DANN	Benign	0.89
PhyloP100		0.51
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: rs57360986; hg19: chr17-6355097;