Genetic Variant SMARCD1:p.Leu48Pro (chr12-50085512-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003076.5(SMARCD1):c.143T>C(p.Leu48Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMARCD1
NM_003076.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

SMARCD1 (HGNC:11106): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD1	NM_003076.5 link	c.143T>C	p.Leu48Pro	missense_variant	Exon 1 of 13	ENST00000394963.9	NP_003067.3	Q96GM5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD1	ENST00000394963.9 link	c.143T>C	p.Leu48Pro	missense_variant	Exon 1 of 13	1	NM_003076.5	ENSP00000378414.4		Q96GM5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1086074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

513670

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.143T>C (p.L48P) alteration is located in exon 1 (coding exon 1) of the SMARCD1 gene. This alteration results from a T to C substitution at nucleotide position 143, causing the leucine (L) at amino acid position 48 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.053

T;.;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Pathogenic

1.0

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.69

N;N;.;.

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.76

N;N;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.36

T;T;T;D

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.0

B;D;.;.

Vest4

0.61

MutPred

0.24

Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);

MVP

0.78

MPC

2.2

ClinPred

0.70

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.49

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over