rs11042

Variant names:

• chr16-3022778-G-A
• rs11042
• NM_017885.4:c.*85C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017885.4(HCFC1R1):​c.*85C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCFC1R1 NM_017885.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 2 publications found

Genes affected

HCFC1R1 (HGNC:21198): (host cell factor C1 regulator 1) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

THOC6 (HGNC:28369): (THO complex subunit 6) This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome. [provided by RefSeq, Dec 2016]

THOC6 Gene-Disease associations (from GenCC):

• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017885.4. 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
	HCFC1R1	NM_017885.4	MANE Select	c.*85C>T		3_prime_UTR	Exon 4 of 4	NP_060355.1	Q9NWW0-1
	HCFC1R1	NM_001002018.2		c.*85C>T		3_prime_UTR	Exon 5 of 5	NP_001002018.1	Q9NWW0-1
	HCFC1R1	NM_001288665.1		c.*85C>T		3_prime_UTR	Exon 5 of 5	NP_001275594.1	Q9NWW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCFC1R1	ENST00000248089.8	TSL:1 MANE Select	c.*85C>T		3_prime_UTR	Exon 4 of 4	ENSP00000248089.4	Q9NWW0-1
	HCFC1R1	ENST00000574151.5	TSL:1	c.*85C>T		3_prime_UTR	Exon 3 of 3	ENSP00000459178.1	Q9NWW0-2
	HCFC1R1	ENST00000576921.1	TSL:1	n.1046C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1098740 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 534852

African (AFR) AF: 0.00 AC: 0 AN: 21264

American (AMR) AF: 0.00 AC: 0 AN: 10894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16866

East Asian (EAS) AF: 0.00 AC: 0 AN: 26894

South Asian (SAS) AF: 0.00 AC: 0 AN: 47946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 878328

Other (OTH) AF: 0.00 AC: 0 AN: 46554

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.50
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11042; hg19: chr16-3072779;