rs781412352

Variant names:

• chr15-66490490-C-A
• rs781412352
• NM_002755.4:c.1069-12C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-66490490-C-A
• chr15-66490490-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006049.4(SNAPC5):​c.*249G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,584,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: SNAPC5 NM_006049.4 3_prime_UTR
• Scores: Splicing: ADA: 0.0003367
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.757
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-66490490-C-A is Benign according to our data. Variant chr15-66490490-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1902241.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1069-12C>A		intron	N/A	NP_002746.1	Q02750-1
	SNAPC5	NM_006049.4		c.*249G>T		3_prime_UTR	Exon 4 of 4	NP_006040.1	O75971-1
	MAP2K1	NM_001411065.1		c.925-12C>A		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.1069-12C>A		intron	N/A	ENSP00000302486.5	Q02750-1
	ENSG00000261351	ENST00000565387.2	TSL:1	n.336G>T		non_coding_transcript_exon	Exon 2 of 2
	SNAPC5	ENST00000395589.6	TSL:2	c.*249G>T		3_prime_UTR	Exon 4 of 4	ENSP00000378954.2	O75971-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251440 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000230 AC: 33 AN: 1431926 Hom.: 1 Cov.: 26 AF XY: 0.0000308 AC XY: 22 AN XY: 714248

African (AFR) AF: 0.00 AC: 0 AN: 32830

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.000327 AC: 28 AN: 85662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5716

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1084806

Other (OTH) AF: 0.0000169 AC: 1 AN: 59272

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	RASopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.72
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.082
SpliceAI score (max)		0.030		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: rs781412352; hg19: chr15-66782828;