rs397516788

Variant names:

• chr15-66489770-CTATT-C
• rs397516788
• NM_002755.4:c.1068+12_1068+15delTATT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006049.4(SNAPC5):​c.*965_*968delAATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,610,934 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (7 hom.)
• Consequence: SNAPC5 NM_006049.4 3_prime_UTR
• Clinical Significance: Benign reviewed by expert panel U:2 B:12
• Conservation: PhyloP100: -0.0830
• Publications: 2 publications found

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

ENSG00000261351 (HGNC:):

SNAPC5 (HGNC:15484): (small nuclear RNA activating complex polypeptide 5) This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant 15-66489770-CTATT-C is Benign according to our data. Variant chr15-66489770-CTATT-C is described in ClinVar as Benign. ClinVar VariationId is 44586.Status of the report is reviewed_by_expert_panel, 3 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006049.4. 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
	MAP2K1	NM_002755.4	MANE Select	c.1068+12_1068+15delTATT		intron	N/A	NP_002746.1	Q02750-1
	SNAPC5	NM_006049.4		c.*965_*968delAATA		3_prime_UTR	Exon 4 of 4	NP_006040.1	O75971-1
	MAP2K1	NM_001411065.1		c.924+12_924+15delTATT		intron	N/A	NP_001397994.1	A0A8I5KYS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K1	ENST00000307102.10	TSL:1 MANE Select	c.1068+12_1068+15delTATT		intron	N/A	ENSP00000302486.5	Q02750-1
	ENSG00000261351	ENST00000565387.2	TSL:1	n.1052_1055delAATA		non_coding_transcript_exon	Exon 2 of 2
	MAP2K1	ENST00000685172.1		c.1022+499_1022+502delTATT		intron	N/A	ENSP00000509604.1	A0A8I5KYB4

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 340 AN: 152210 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00223 AC: 560 AN: 251462 AF XY: 0.00223

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00355

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00304 AC: 4427 AN: 1458606 Hom.: 7 AF XY: 0.00298 AC XY: 2162 AN XY: 725872

African (AFR) AF: 0.000538 AC: 18 AN: 33428

American (AMR) AF: 0.00210 AC: 94 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00655 AC: 171 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86206

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53406

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00358 AC: 3965 AN: 1108976

Other (OTH) AF: 0.00260 AC: 157 AN: 60312

GnomAD4 genome AF: 0.00223 AC: 340 AN: 152328 Hom.: 2 Cov.: 32 AF XY: 0.00207 AC XY: 154 AN XY: 74494

African (AFR) AF: 0.000722 AC: 30 AN: 41574

American (AMR) AF: 0.00294 AC: 45 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00338 AC: 230 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00327 Hom.: 0

Bravo AF: 0.00248

EpiCase AF: 0.00469

EpiControl AF: 0.00456

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	3	RASopathy (3)
-	1	1	Noonan syndrome (2)
-	1	-	Cardio-facio-cutaneous syndrome (1)
-	-	1	Noonan syndrome and Noonan-related syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.083
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: rs397516788; hg19: chr15-66782108; COSMIC: COSV104596930;