NM_015295.3:c.*1579G>A

Variant names:

• chr18-2804131-G-A
• rs559994
• NM_015295.3:c.*1579G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015295.3(SMCHD1):​c.*1579G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,008 control chromosomes in the GnomAD database, including 9,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9114 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SMCHD1 NM_015295.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 7 publications found

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]

SMCHD1 Gene-Disease associations (from GenCC):

• arhinia, choanal atresia, and microphthalmia

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, ClinGen, Illumina
• facioscapulohumeral muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000266049 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015295.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCHD1	NM_015295.3	MANE Select	c.*1579G>A		3_prime_UTR	Exon 48 of 48	NP_056110.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMCHD1	ENST00000320876.11	TSL:5 MANE Select	c.*1579G>A		3_prime_UTR	Exon 48 of 48	ENSP00000326603.7
	ENSG00000266049	ENST00000583546.1	TSL:3	n.370+4324C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48073 AN: 151890 Hom.: 9118 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.318

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.316 AC: 48066 AN: 152008 Hom.: 9114 Cov.: 32 AF XY: 0.316 AC XY: 23499 AN XY: 74284

African (AFR) AF: 0.112 AC: 4640 AN: 41500

American (AMR) AF: 0.365 AC: 5569 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3464

East Asian (EAS) AF: 0.192 AC: 996 AN: 5178

South Asian (SAS) AF: 0.185 AC: 891 AN: 4826

European-Finnish (FIN) AF: 0.436 AC: 4589 AN: 10524

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29245 AN: 67954

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.387 Hom.: 15338

Bravo AF: 0.299

Asia WGS AF: 0.164 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.44
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs559994; hg19: chr18-2804129;