rs147034750

Variant names:

• chr18-2769782-C-A
• NM_015295.3:c.4808C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-2769782-C-A
• chr18-2769782-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_015295.3(SMCHD1):​c.4808C>A​(p.Thr1603Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SMCHD1 NM_015295.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]

ENSG00000266049 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the SMCHD1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 10 curated benign missense variants. Gene score misZ: 3.6318 (above the threshold of 3.09). Trascript score misZ: 3.965 (above the threshold of 3.09). GenCC associations: The gene is linked to facioscapulohumeral muscular dystrophy, arhinia, choanal atresia, and microphthalmia, hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.051685244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMCHD1	NM_015295.3	c.4808C>A	p.Thr1603Asn	missense_variant	Exon 38 of 48	ENST00000320876.11	NP_056110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMCHD1	ENST00000320876.11	c.4808C>A	p.Thr1603Asn	missense_variant	Exon 38 of 48	5	NM_015295.3	ENSP00000326603.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452788 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721760

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.66
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.036
Sift	Benign	0.49	T
Sift4G	Benign	0.49	T
Polyphen		0.010	B
Vest4		0.31
MutPred		0.22		Loss of phosphorylation at T1603 (P = 0.0953);
MVP		0.068
MPC		0.25
ClinPred		0.050	T
GERP RS		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.24

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.

Other links and lift over

hg19: chr18-2769780;