7-551426-G-A

Variant names:

• chr7-551426-G-A
• rs144431535
• NM_001164760.2:c.936C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The NM_001164760.2(PRKAR1B):​c.936C>T​(p.Tyr312Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000814 in 1,560,538 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (2 hom.)
• Consequence: PRKAR1B NM_001164760.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.10
• Publications: 0 publications found

Genes affected

PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]

PRKAR1B Gene-Disease associations (from GenCC):

• Marbach-Schaaf neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• PRKAR1B-related neurodegenerative dementia with intermediate filaments

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP6: Variant 7-551426-G-A is Benign according to our data. Variant chr7-551426-G-A is described in ClinVar as Benign. ClinVar VariationId is 782256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS2: High AC in GnomAd4 at 562 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164760.2. 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
	PRKAR1B	NM_001164760.2	MANE Select	c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	NP_001158232.1	P31321
	PRKAR1B	NM_001164758.2		c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	NP_001158230.1	P31321
	PRKAR1B	NM_001164759.1		c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	NP_001158231.1	P31321

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR1B	ENST00000537384.6	TSL:5 MANE Select	c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	ENSP00000440449.1	P31321
	PRKAR1B	ENST00000360274.8	TSL:1	c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	ENSP00000353415.4	P31321
	PRKAR1B	ENST00000403562.5	TSL:1	c.936C>T	p.Tyr312Tyr	synonymous	Exon 10 of 11	ENSP00000385349.1	P31321

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 556 AN: 152076 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000975 AC: 164 AN: 168218 AF XY: 0.000747

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000513

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000900

Gnomad FIN exome AF: 0.0000632

Gnomad NFE exome AF: 0.0000600

Gnomad OTH exome AF: 0.000436

GnomAD4 exome AF: 0.000503 AC: 709 AN: 1408344 Hom.: 2 Cov.: 31 AF XY: 0.000457 AC XY: 318 AN XY: 695486

African (AFR) AF: 0.0115 AC: 375 AN: 32742

American (AMR) AF: 0.000716 AC: 26 AN: 36334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00487 AC: 183 AN: 37604

South Asian (SAS) AF: 0.000312 AC: 25 AN: 80040

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48422

Middle Eastern (MID) AF: 0.00127 AC: 7 AN: 5526

European-Non Finnish (NFE) AF: 0.0000286 AC: 31 AN: 1084138

Other (OTH) AF: 0.00105 AC: 61 AN: 58370

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152194 Hom.: 4 Cov.: 33 AF XY: 0.00370 AC XY: 275 AN XY: 74412

African (AFR) AF: 0.0124 AC: 513 AN: 41502

American (AMR) AF: 0.00170 AC: 26 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67978

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00157 Hom.: 1

Bravo AF: 0.00389

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PRKAR1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.44
DANN	Benign	0.91
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144431535; hg19: chr7-591063;