chr14-54568111-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015589.6(SAMD4A):​c.195C>T​(p.Pro65=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,513,208 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

SAMD4A
NM_015589.6 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00007261
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.35
Variant links:
Genes affected
SAMD4A (HGNC:23023): (sterile alpha motif domain containing 4A) Sterile alpha motifs (SAMs) in proteins such as SAMD4A are part of an RNA-binding domain that functions as a posttranscriptional regulator by binding to an RNA sequence motif known as the Smaug recognition element, which was named after the Drosophila Smaug protein (Baez and Boccaccio, 2005 [PubMed 16221671]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 14-54568111-C-T is Benign according to our data. Variant chr14-54568111-C-T is described in ClinVar as [Benign]. Clinvar id is 711102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-54568111-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.35 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00524 (798/152198) while in subpopulation AFR AF= 0.0181 (753/41514). AF 95% confidence interval is 0.0171. There are 11 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 798 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAMD4ANM_015589.6 linkuse as main transcriptc.195C>T p.Pro65= splice_region_variant, synonymous_variant 2/13 ENST00000554335.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAMD4AENST00000554335.6 linkuse as main transcriptc.195C>T p.Pro65= splice_region_variant, synonymous_variant 2/135 NM_015589.6 A1Q9UPU9-1

Frequencies

GnomAD3 genomes
AF:
0.00521
AC:
793
AN:
152094
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0181
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00109
AC:
137
AN:
125946
Hom.:
2
AF XY:
0.000883
AC XY:
62
AN XY:
70220
show subpopulations
Gnomad AFR exome
AF:
0.0254
Gnomad AMR exome
AF:
0.000761
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000878
Gnomad OTH exome
AF:
0.000852
GnomAD4 exome
AF:
0.000523
AC:
712
AN:
1361010
Hom.:
5
Cov.:
32
AF XY:
0.000450
AC XY:
302
AN XY:
670738
show subpopulations
Gnomad4 AFR exome
AF:
0.0188
Gnomad4 AMR exome
AF:
0.00114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000647
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000551
Gnomad4 OTH exome
AF:
0.00127
GnomAD4 genome
AF:
0.00524
AC:
798
AN:
152198
Hom.:
11
Cov.:
32
AF XY:
0.00520
AC XY:
387
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0181
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.00603

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 13, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
1.9
DANN
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000073
dbscSNV1_RF
Benign
0.11
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200235203; hg19: chr14-55034829; API